B cell lymphoma mutations, compositions, and uses to enhance engineered t cell therapies

Abstract

The present disclosure relates generally to mutations in B cell lymphoma, and methods of use of the mutations in T cell therapy.

Description

Atty. Dkt. No.: 121384-0284B CELL LYMPHOMA MUTATIONS, COMPOSITIONS, AND USES TO ENHANCE ENGINEERED T CELL THERAPIESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional Application No. 63 / 695,340, filed September 16, 2024, the entire contents of which are incorporated herein by reference.STATEMENT OF GOVERNMENT SUPPORT

[0002] This invention was made with government support under grant number CA288003 awarded by the National Institutes of Health. The government has certain rights in the invention.FIELD

[0003] The present invention relates generally to T cell therapy. The disclosure provides vectors and engineered cells comprising polypeptides which enhance T cell persistence in cancer tells, the tumor microenvironment, and tumor draining lymph nodes. Also provided herein are methods for generating the engineered cells and therapeutic methods of use.BACKGROUND

[0004] The following description of the background of the present technology is provided simply as an aid in understanding the present technology and is not admitted to describe or constitute prior art to the present technology.

[0005] Adoptive and engineered T cell therapies, including chimeric antigen receptor (CAR) T cells, T cell receptor (TCR) engineered T cells, have emerged recently as important therapies for cancer, inflammation and infectious diseases. In adoptive cell therapy, infusions of T cells are used to recognize and eliminate tumor cells.

[0006] Current limitations in adoptive T cell therapy to treat cancer include fitness of T cells, persistence of T cells, and immunosuppressive environmental factors. Thus, the identification-1-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 and use of enhanced T cell therapies are needed for therapeutic purposes. This disclosure provides composition and methods that meet this need.SUMMARY

[0007] According to one embodiment, provided herein is a vector comprising a nucleic acid sequence encoding a polypeptide, the polypeptide comprising at least one B cell lymphoma wild-type or mutant protein or functional fragment thereof. In one aspect, the vector is selected from a plasmid, a herpes simplex virus, a retrovirus, an adenovirus, or an adeno- associated virus. In one aspect the retrovirus is a lentivirus.

[0008] According to another embodiment, provided herein is an engineered cell comprising a polypeptide or nucleotide encoding a polypeptide comprising at least one B cell lymphoma protein mutation or functional fragment thereof.

[0009] In some aspects, the polypeptide of the vector or engineered cell comprises at least one selected from a BCLIO, CTSS, ShAPI2-MALTl, API2-MALT1 HNRNPD, FOXO1, MEF2C, HIST1H1E, IRF8, HRAS, MEF2B, BTK, IKBKB, BCL2, CARD11, MYD88, KLF2, MYC, IGH, PIK3CD, PIM2, MAP2K1, OSBPL10, FOXP1, TNRFSF14, CD79B, HIST1H2BC, STAT6, SGK1, RRAGC, EGR1, BTG1, DIS3, ETNK1, ETS1, EZH2, HIST1H1D, IKZF3, IRF4, KLHL6, MAP2K2, mCXCR4, mIL4R, NKAP, PIM1, PPP4C, RFTN1, SOCS1, TBL1XR1, TLR2, USP8, ZBTB7A, or ZFP36Ll, protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wildtype protein. In some other aspects, the polypeptide comprises at a BCL2, CXCR4, mPDCDl, MYD88, RRAGC, TBL1XR1, tCD19, tCD20, MYC, FOXP1, or XPO1 wild-type protein.10010] In one aspect the variant comprises a single-point, double-point, insertion, or fusion mutation of the wild-type protein.

[0011] In one aspect, the engineered cell comprises the vector described herein.10012] In one aspect, the engineered cell is a T cell. In one aspect, the engineered cell comprises a receptor with specificity for a target antigen.-2-4919-8127-7289.1Atty. Dkt. No.: 121384-0284[0013| In some embodiments, the protein in the vector or engineered cell provided herein is selected from a variant presented in Tables 1 or 5. In some embodiments, the protein in the vector or engineered cell is encoded by a sequence selected from SEQ ID NOs: 1-70, 79-81.

[0014] In some embodiments, the wild-type or variant is selected from: a BCL10 substitution at amino acid 58, 140, or 209; BCL10 wild-type; CTSS substitution at amino acid 132; ShAPI2-MALTl fusion; API2-MALT1 fusion; HNRNPD substitution at amino acid 48; FOXO1 substitution at amino acid 24; MEF2C substitution at amino acid 389; HIST1H1E substitution at amino acid 158; IRF8 substitution at amino acid 23; HRAS substitution at amino acid 145; MEF2B substitution at amino acid 83; BTK substitution at amino acid 474 and 513; IKBKB substitution at amino acid 171; BCL2 substitution at amino acid 7 or 33; CARD11 substitution at amino acid 49; MYD88 substitution at amino acid 265; KLF2 substitution at amino acid 291; MYC-IGH / MYC fusion; PIK3CD substitution at amino acid 1021; PIM2 substitution at amino acid 27 or 31; MAP2K1 substitution at amino acid 53; OSBPL10 substitution at amino acid 94; IGH-FOXP1 / FOXP1 fusion; TNRFSF14 substitution at amino acid 135; CD79B substitution at amino acid 196; HIST1H2BC substitution at amino acid 63; STAT6 substitution at amino acid 419; SGK1 substitution at amino acid 143; RRAGC substitution at amino acid 90; EGR1 substitution at amino acid 34; ATP6V1B2 substitution at amino acid 371 or 400; BTG1 substitution at amino acid 36; CXCR4 wild-type; DIS3 substitution at amino acid 488; ETNK1 substitution at amino acid 244; ETS1 substitution at amino acid 23; EZH2 substitution at amino acid 113 or 646; HIST1H1D substitution at amino acid 186; IKZF3 substitution at amino acid 162; IRF4 substitution at amino acid 66; KLHL6 substitution at amino acid 90; MAP2K2 substitution at amino acid 60; mCXCR4 substitution at amino acid 345; mIL4R substitution at amino acid 243; mPDCDl wild-type; MYD88 wild-type; NKAP substitution at amino acid 405; PIM1 substitution at amino acid 81; PIM2 substitution at amino acid 31; PPP4C substitution at amino acid 54; PTPN11 wild-type; RFTN1 substitution at amino acid 255; SOCS1 substitution at amino acid 17; TBL1XR1 substitution at amino acid 446 or wild-type; tCD19 wild-type; tCD20 wild-type; TLR2 substitution at amino acid 327; USP8 substitution at amino acid 657; XPO1 wild-type; ZBTB7A substitution at amino acid 247; MYC wild-type; FOXP1 wild-type; and / or ZFP36L1 substitution at amino acid 19.-3-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0015] In one aspect, the engineered cell has increased or decreased signaling through the API, NF AT, NFKB, and / or PD1 pathways. In another aspect, the engineered cell has increased or decreased cytokine production. The cytokine can be selected from IL-2, IL-4, II- 5, TNF alpha, IFN- gamma and / or IL-13.10016] Also provided herein is a composition comprising the engineered cell and a pharmaceutically acceptable carrier.

[0017] Also provided herein are methods to increase the persistence of T cells in a cancer cell or tumor, comprising contacting the cancer cells or tumor with the engineered cell or composition described herein. In some aspects, the contacting is in vivo or in vitro.

[0018] Also provided herein are methods of treatment or therapeutic use in a subject in need thereof.

[0019] In one aspect, provided herein is a method to increase the persistence of T cells in a tumor microenvironment or tumor draining lymph nodes of a subject in need thereof, comprising administering to the subject in the engineered cell or composition described herein.

[0020] In one aspect, provided herein is a method to prevent tumor recurrence in a subject in need thereof, comprising administering to the subject in the engineered cell or composition described herein after a subject has reduced tumor growth or symptoms. In one aspect the subject is in partial or complete remission.

[0021] In another aspect, provided herein is a to inhibit the growth of a cancer and / or increase the survival rate of a subject in need thereof, comprising administering to the subject in the engineered cell or composition described herein.J0022] In another aspect, provided herein is a method to inhibit the growth of a first cancer and / or increase the survival rate of a subject in need, comprising administering to the subject in need the engineered cell or composition, wherein growth of a second cancer is also inhibited after the first cancer is contacted with the engineered cell or composition, and wherein the first cancer comprises an antigen recognized by the engineered cell. The first-4-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 cancer and the second cancer may be the same, related, or different. In one aspect, the second cancer is a metastasis of the first cancer. In one aspect, the first cancer is positive for a T-cell dependent antigen and the second cancer is negative for the T-cell dependent antigen.

[0023] In the methods of treatment described herein, the cancer, including the first and / or second cancer, may be a solid tumor. The cancer, including the first and / or second cancer, may be a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, nonsmall cell king cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.

[0024] In the methods of treatment described herein, the engineered cell or composition maybe administered parenterally (including intramuscularly, subcutaneously, intradermally, intravascularly, intravenously, intraarterially, intramedullary and intrathecally), intraperitoneally, or intratumorally. In the methods of treatment described herein, the subject in need may- be a mammal, optionally a human.

[0025] According to one embodiment, provided herein is a method to generate a vector, comprising transferring a plasmid to a cell, wherein the plasmid comprises a nucleotide encoding a polypeptide comprising at least one least one B cell lymphoma protein mutation or functional fragment thereof. The nucleotide may have a sequence according to one or more selected from SEQ ID NOs: 1-70, 79-81. In some aspects, the vector is a retrovirus, optionally a lentivirus.

[0026] Kits containing the engineered cells and compositions described herein are also provided.BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 shows an exemplary B Cell Lymphoma Mutation Library. AA change indicates the type of mutation. For example, V600E indicates a substitution of V with E at amino acid 600. The variants follow conventional nomenclature of proteins, as taught for-5-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 example in https: / / atlasgeneticsoncology.org / teaching / 30067 / nomenclature-for-the- description-of-mutations-and-other-sequence-variations the entire contents of which are incorporated by reference.

[0028] Figure 2 shows the B Cell Lymphoma Mutation screening protocol.

[0029] Figure 3 shows the enrichment of B Cell Lymphoma mutation library TILs compared to control OT-1 at Day 7 after T cell transfer. ****p<0.0001 unpaired t test. TIL is tumorinfiltrate lymphocytes. TILs are a measurement of persistence in the tumor on day 7 after T cell transfer.

[0030] Figure 4 shows the BCL pooled log2 tumor fold change. 2 OT-1+ CD8+ T cells were transduced with a pool of viruses encoding a library of B cell lymphoma mutations. T cells were transferred into mice with B16-F10-OVA tumors. After 7 days T cells were collected from the tumors and the abundance was determined by sequencing. Two replicate experiments are plotted. The higher log2fold change indicates increased persistence in the tumor.[0031 Figures 5A-5C. BCL mutants enhance CAR T cell signaling activation and IL2 production. (FIG. 5A) Mutations were introduced in Jurkat CAR T cells. Cells were cocultured with K562-CD19 target cells for 24 hours. IL2 secretion (FIG. 5B) was measured by ELISA and T cell activation was measured by using fluorescent reporters for NFKB, API and NF AT (FIG. 5C).

[0032] Figure 6. BCL mutants enhance CAR T proliferation in vitro. CD3+ primary human T cells from 3 donors were transduced with CD 19 BBz CAR and indicated mutations. CAR T cells were incubated with A375 cells expressing CD19 at a 2: 1 T cell to tumor cell ratio. Every 3 days the CAR T cells were collected and added to fresh A375-CD19 cells at 2: 1 ratio and the cell proliferation was measured. Points represent the average of 3 donors * p<0.05 for paired ratio t test.

[0033] Figure 7. Diffuse large B cell lymphoma mutation MyD88 L265P T cell enrichment. Dual transfer competition assay in a B16-F10 / pmel model shows 7 fold enrichment of Myd88 L265P expressing CD8 T cells compared to vector controls on Day 7.-6-4919-8127-7289.1Atty. Dkt. No.: 121384-0284[0034| Figure 8 shows a schematic of tumor challenge in mice.

[0035] Figures 9A-9E. BCL10 E140X. (FIG. 9A). Schematic of timeline of tumor model. (FIG. 9B). Validation of BCL10 E140X in B16-F10 OVA models shows tumor clearance with treatment of IM BCL10 E140X expressing OT-1 CD8 T cells. (FIG. 9C). Peripheral tail vein sampling shows expansion of fusion cells in the blood in an antigen dependent manner. (FIG. 9D) Survival curves of mice treated with BCL10 E140X. (FIG. 9E). Fold enrichment of BCL10 E140X TILs compared to OT-1 control Day 7 after T cell transfer. **** p<o 0001 for unpaired t test, **p<0.01 for survival analysis.

[0036] Figures 10A-10C. Re-challenge with BCL10 E140X. (FIG. 10A) B16-OVA tumor rechallenge on contralateral flank at Day 60. (FIG. 10B). B16-F10 tumor rechallenge on Day 60. (FIG. 10C). Tail vein blood samples every 3-4 days after Day 60 double tumor rechallenge.

[0037] Figures 11A-11E. BCL10 R58Q. (FIG. 11 A). Schematic of timeline of tumor model. (FIG. 11B). Validation of BCL10 R58Q in B16-F10 OVA models shows tumor clearance with treatment of IM of BCL10 R58Q expressing OT-1 CD8 T cells. (FIG. 11C). Peripheral tail vein sampling shows expansion of fusion cells in the blood in an antigen dependent manner. (FIG. 11D). Survival curves of mice treated with of BCL10 R58Q. (FIG. HE). Fold enrichment of BCL10 R58Q TILs compared to OT-1 control Day 7 after T cell transfer. **** p<0.0001 for unpaired t test, **p<0.01 for survival analysis.

[0638] Figures 12. BCL10 R58Q mutant increases tumor infiltrating T cell abundance.

[0039] Figures 13A-13C Re-challenge with BCL10 R58Q. (FIG. 13A) B16-OVA tumor rechallenge on contralateral flank at Day 60. (FIG. 13B). B16-F10 tumor rechallenge on Day 60. (FIG. 13C). Tail vein blood samples every 3-4 days after Day 60 double tumor rechallenge.

[0040] Figures 14A-14D. Double Mutant BCL10 R58Q E140X. (FIG. 14A) Schematic of timeline of tumor model. (FIG. 14B). Validation of BCL10 R58Q E140X double mutant in B16-F10 OVA models shows tumor clearance with treatment of IM BCL10 R58Q E140X double mutant expressing OT-1 CD8 T cells. (FIG. 14C). Peripheral tail vein sampling-7-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 shows expansion of fusion cells in the blood in an antigen dependent manner. (FIG. 14D). Survival curves of mice treated with BCL10 R58Q E140X double mutant * p<0.05 for survival analysis.

[0041] Figures 15A-15E. MYD88 L265P. (FIG. 15A). Schematic of timeline of tumor model. (FIG. 15B). Validation of MYD88 L265P in B16-F10 OVA models shows tumor clearance with treatment of IM MYD88 L265P expressing OT-1 CD8 T cells. (FIG. 15C). Peripheral tail vein sampling shows expansion of fusion cells in the blood in an antigen dependent manner. (FIG. 15D). Survival curves of mice treated with MYD88 L265P. (FIG. 15E). Fold enrichment of MYD88 L265P TILs compared to OT-1 control Day 7 after T cell transfer. **** p<0.0001 for unpaired t test, **p<0.01 for survival analysis.[00421 Figures 16A-16C Re-challenge with MYD88 L265P. (FIG. 16A) B16-OVA tumor rechallenge on contralateral flank at Day 60. (FIG. 16B). B16-F10 tumor rechallenge on Day 60. (FIG. 16C). Tail vein blood samples every 3-4 days after Day 60 double tumor rechallenge.[0043[ Figures 17A-17C. IKBKB K171T. (FIG. 17A). Validation of IKBKB K171T in B16-F10 OVA models shows tumor clearance with treatment of 100k IKBKB K171T (unsorted) expressing OT-1 CD8 T cells. (FIG. 17B). Survival curves of mice treated with IKBKB K171T. (FIG. 17C). Fold enrichment of IKBKB K171T TILs and TdLN accumulation compared to OT-1 control Day 7 after T cell transfer. **** p<0.0001, **p<0.001 for unpaired t test, **p<0.01 for survival analysis.

[0044] Figures 18A-18B. PMEL + / - BCL10 R58Q. (FIG. 18A). Growth curves of B16-F10 tumors treated with adoptive T cell transfer. 5xl05B16-F10 cells were injected subcutaneously into C57BL / 6 mice at day 0, T cells were transferred in indicated amounts by retro orbital injection at day 7. Dotted lines are individual tumors, solid lines show the average of 9 tumors. (FIG. 18B). Survival curves of mice from A, mice survival was based on mouse death or tumors reaching a maximum size of 1.5cm in one dimension.

[0045] Figure 19 shows differential expression of cytokine genes in CD8+ T cells isolated from OT-I TCR transgenic mice and transduced with an MSCV retrovirus encoding genes listed in the figure.-8-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0046] Figure 20 shows differential expression of chemokines / chemokine receptor genes in CD8+ T cells isolated from OT-I TCR transgenic mice and transduced with an MSCV retrovirus encoding genes listed in the figure.

[0047] Figure 21 shows differential expression of cytokine genes in CD3+ T cells from healthy donors and transduced with lentivirus encoding genes listed in the figure.

[0048] Figure 22 shows differential expression of chemokines / chemokine receptor genes in CD3+ T cells from healthy donors and transduced with lentivirus encoding genes listed in the figure.

[0049] Figure 23 shows results of tumor volume (left) and survival curves (right) upon administration of CAR + BTK T474M E513G T cells compared to controls in NSG mice injected with A375 -CD 19 cells.

[0050] Figure 24 shows results of tumor volume (left) and survival curves (right) upon administration of CAR + BTK T474M E513G T cells compared to controls in NSG mice injected with U375 cells.DETAILED DESCRIPTION

[0051] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the present application and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. While not explicitly defined below, such terms should be interpreted according to their common meaning.

[0052] The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.-9-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0053] Unless explicitly indicated otherwise, all specified embodiments, features, and terms intend to include both the recited embodiment, feature, or term and biological equivalents thereof.Definitions

[0054] Unless otherwise specified “a” or “an” means one or more.

[0055] All numeric values should be treated as having the term “about” placed before a specific numeric value.

[0056] As used herein, the term “about” placed before a specific numeric value may mean ±20% of the numeric value; ±18% of the numeric value, ±15% of the numeric value; ±12% of the numeric value; ±8% of the numeric value; ±5% of the numeric value; ±3% of the numeric value; ±2% of the numeric value; ±1% of the numeric value or ±0.5% of the numeric value.

[0057] “Optional” or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not.

[0058] As used herein, “and / or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”).

[0059] As used herein, the term “comprising” is intended to mean that the compounds, compositions and methods include the recited elements, but not exclude others. “Consisting essentially of’ when used to define compounds, compositions and methods, shall mean excluding other elements of any essential significance to the combination. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants, e.g., from the isolation and purification method and pharmaceutically acceptable carriers, preservatives, and the like. “Consisting of’ shall mean excluding more than trace elements of other ingredients. Embodiments defined by each of these transition terms are within the scope of this technology.-10-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0060] In some embodiments, the term “engineered” or “recombinant” refers to having at least one modification not normally found in a naturally occurring protein, polypeptide, polynucleotide, strain, wild-type strain or the parental host strain of the referenced species. In some embodiments, the term “engineered” or “recombinant” refers to being synthetized by human intervention. As used herein, the term “recombinant protein” refers to a polypeptide which is produced by recombinant DNA techniques, wherein generally, DNA encoding the polypeptide is inserted into a suitable expression vector which is in turn used to transform a host cell to produce the heterologous protein.

[0061] The terms “polynucleotide”, “nucleic acid” and “oligonucleotide” are used interchangeably and refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides or analogs thereof. Polynucleotides can have any three dimensional structure and may perform any function, known or unknown. The following are non limiting examples of polynucleotides: a gene or gene fragment (for example, a probe, primer, EST or SAGE tag), exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes and primers. A polynucleotide can comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure can be imparted before or after assembly of the polynucleotide. The sequence of nucleotides can be interrupted by non nucleotide components. A polynucleotide can be further modified after polymerization, such as by conjugation with a labeling component. The term also refers to both double and single stranded molecules. Unless otherwise specified or required, any embodiment of this disclosure that is a polynucleotide encompasses both the double stranded form and each of two complementary single stranded forms known or predicted to make up the double stranded form.

[0062] A polynucleotide is composed of a specific sequence of four nucleotide bases: adenine (A); cytosine (C); guanine (G); thymine (T); and uracil (U) for thymine when the polynucleotide is RNA. Thus, the term “polynucleotide sequence” is the alphabetical representation of a polynucleotide molecule. This alphabetical representation can be input-11-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 into databases in a computer having a central processing unit and used for bioinformatics applications such as functional genomics and homology searching.(0063] A “gene” refers to a polynucleotide containing at least one open reading frame (ORF) that is capable of encoding a particular polypeptide or protein after being transcribed and translated.

[0064] The term “express” refers to the production of a gene product, such as mRNA, peptides, polypeptides or proteins. As used herein, “expression” refers to the process by which polynucleotides are transcribed into mRNA or the process by which the transcribed mRNA is subsequently being translated into peptides, polypeptides, or proteins. If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

[0065] As used herein, the term “overexpress” intends a level of expression of the mRNA, the protein or the polypeptide” that is greater than or exceeds the level of expression of the mRNA, the protein or the polypeptide in a native, wild-type or cell that has not been engineered to increase expression.

[0066] A “gene product” or alternatively a “gene expression product” refers to the amino acid (e.g., peptide or polypeptide) generated when a gene is transcribed and translated. In some embodiments, the gene product may refer to an mRNA or other RNA, such as an interfering RNA, generated when a gene is transcribed.

[0067] The term “encode” as it is applied to polynucleotides refers to a polynucleotide which is said to “encode” a polypeptide if, in its native state or when manipulated by methods well known to those skilled in the art, it can be transcribed to produce the mRNA for the polypeptide or a fragment thereof, and optionally translated to produce the polypeptide or a fragment thereof. The antisense strand is the complement of such a nucleic acid, and the encoding sequence can be deduced therefrom. Further, as used herein an amino acid sequence coding sequence refers to a nucleotide sequence encoding the amino acid sequence.

[0068] The term “a regulatory sequence”, “an expression control element” or “promoter” as used herein, intends a polynucleotide that is operatively linked to a target polynucleotide to-12-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 be transcribed or replicated, and facilitates the expression or replication of the target polynucleotide. A promoter is an example of an expression control element or a regulatory sequence. Promoters can be located 5’ or upstream of a gene or other polynucleotide, that provides a control point for regulated gene transcription. Polymerase II and III are examples of promoters. In some embodiments, a regulatory sequence is bidirectional, i.e., acting as a regulatory sequence for the coding sequences on both sides of the regulatory sequence. Such bidirectional regulatory sequence may comprise, or consists essentially of, or consists of a bidirectional promoter (see for example Trinklein ND, et al. (2004) An abundance of bidirectional promoters in the human genome. Genome Res. Jan;14(l):62-6).

[0069] The term “protein,” “peptide” and “polypeptide” are used interchangeably and in their broadest sense to refer to a compound of two or more subunit amino acids, amino acid analogs or peptidomimetics. The subunits (which are also referred to as residues) may be linked by peptide bonds. In another embodiment, the subunit may be linked by other bonds, e.g., ester, ether, etc. A protein or peptide must contain at least two amino acids and no limitation is placed on the maximum number of amino acids which may comprise a protein's or peptide's sequence. As used herein the term “amino acid” refers to either natural and / or unnatural or synthetic amino acids, including glycine and both the D and L optical isomers, amino acid analogs and peptidomimetics.

[0070] The amino acid single-letter and three-letter codes are found below:Full Name of Amino-Acid Single-Letter Code Three-Letters CodeGlycine G GlyAlanine A AlaLeucine L LeuMethionine M MetPhenylalanine F PheTryptophan W Trp-13-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Lysine K LysGlutamine Q GinGlutamic Acid E GluSerine S SerProline P ProValine V VaiIsoleucine I HeCysteine C CysTyrosine Y TyrHistidine H HisArginine R ArgAsparagine N AsnAspartic Acid D AspThreonine T Thr

[0071] As used herein, the term “antibody” collectively refers to immunoglobulins or immunoglobulin-like molecules including by way of example and without limitation, IgA, IgD, IgE, IgG and IgM, combinations thereof, and similar molecules produced during an immune response in any vertebrate, for example, in mammals such as humans, goats, rabbits and mice, as well as non-mammalian species, such as shark immunoglobulins. Unless specifically noted otherwise, the term “antibody” includes intact immunoglobulins and “antibody fragments” or “antigen binding fragments” that specifically bind to a molecule of interest (or a group of highly similar molecules of interest) to the substantial exclusion of binding to other molecules (for example, antibodies and antibody fragments that have a-14-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 binding constant for the molecule of interest that is at least 103M'1greater, at least 104M'1greater or at least 105M'1greater than a binding constant for other molecules in a biological sample). The term “antibody” also includes genetically engineered forms such as chimeric antibodies (for example, murine or humanized non-primate antibodies), heteroconjugate antibodies (such as, bispecific antibodies). See also, Pierce Catalog and Handbook, 1994- 1995 (Pierce Chemical Co., Rockford, Ill.); Owen et al., Kuby Immunology, 7th Ed., W.H. Freeman & Co., 2013; Murphy, Janeway’s Immunobiology, 8th Ed., Garland Science, 2014; Male et al., Immunology (Roitt), 8th Ed., Saunders, 2012; Parham, The Immune System, 4th Ed., Garland Science, 2014.

[0072] As used herein, the term “T cell,” refers to a type of lymphocyte that matures in the thymus. T cells play an important role in cell-mediated immunity and are distinguished from other lymphocytes, such as B cells, by the presence of a T-cell receptor on the cell surface. T- cells may either be isolated or obtained from a commercially available source. “T cell” includes all types of immune cells expressing CD3 including T-helper cells (CD4+ cells), cytotoxic T-cells (CD8+ cells), natural killer T-cells, T-regulatory cells (Treg) and gammadelta T cells. Additional types of T cells include an invariant natural killer T (iNKT) cell, a mucosal associated invariant T (MAIT) cell, a macrophage, a monocyte, a natural killer (NK) cell, a tumor infiltrating lymphocyte (TIL), a cytotoxic T cell, a T helper cell, a memory T cell, a central memory T (TCM) cell, a stem memory T (TSCM) cell, a stem-cell-like memory T cell (or stem-like memory T cells), an effector memory T (TEM) cell, a TEMRA (CD45RA+) cell, an effector T cell, a Thl cell, a Th2 cell, a Th9 cell, a Th 17 cell, a Th22 cell, a Tfh (follicular helper) cell, a natural killer T (NKT) cell, a transitional memory T (TTM) cell, a terminal effector T (TTE) cell, or a naive T (TN) cell.

[0073] As used herein, the term “sample” refers to clinical samples obtained from a subject. In certain embodiments, a sample is obtained from a biological source (i.e., a “biological sample”), such as tissue, bodily fluid, or microorganisms collected from a subject. Sample sources include, but are not limited to, mucus, sputum, bronchial alveolar lavage (BAL), bronchial wash (BW), whole blood, bodily fluids, cerebrospinal fluid (CSF), urine, plasma, serum, or tissue.-15-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0074] As used herein, the term “stimulation” refers to a primary response induced by binding of a stimulatory molecule (e.g., a TCR / CD3 complex) with its cognate ligand thereby mediating a signal transduction event, such as, but not limited to, signal transduction via the TCR / CD3 complex. Stimulation can mediate altered expression of certain molecules, such as downregulation of TGFP, and / or reorganization of cytoskeletal structures, and the like.

[0075] Transforming growth factor beta (TGF-P) is a cytokine. It can act as an inducer of CXCL13 (Kobayashi et al. (2016) European Journal of Immunology 46(2): 360-71.

[0076] A “stimulatory molecule,” as the term is used herein, means a molecule on a T cell that specifically binds with a cognate stimulatory ligand present on an antigen presenting cell.

[0077] The term “therapeutically effective amount” refers to the amount of the subject compound that will elicit the biological or medical response of a tissue, system, or subject that is being sought by the researcher, veterinarian, medical doctor or other clinician. The term “therapeutically effective amount” includes that amount of a compound that, when administered, is sufficient to prevent development of, or alleviate to some extent, one or more of the signs or symptoms of the disorder or disease being treated. The therapeutically effective amount will vary depending on the compound, the disease and its severity and the age, weight, etc., of the subject to be treated. As used in the methods provided herein, the terms “therapeutically effective amount” and “effective amount” are used interchangeably.

[0078] “Treating” or “treatment” as used herein covers the treatment of a disease or disorder described herein, in a subject, such as a human, and includes: (i) inhibiting a disease or disorder, i.e., arresting its development; (ii) relieving a disease or disorder, i.e., causing regression of the disorder; (iii) slowing progression of the disorder; and / or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the disease or disorder. Therapeutic effects of treatment include, without limitation, inhibiting recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastases, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.

[0079] Treatment of cancer or an infection, immune disorder, or autoimmune response, disorder or disease can be at any time during the cancer or an infection, immune disorder, or -16-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 autoimmune response, disorder or disease. Certain embodiments of the present disclosure can be administered as a combination (e.g., with a second active), or separately concurrently or in sequence (sequentially) in accordance with the methods described herein as a single or multiple dose e.g., one or more times hourly, daily, weekly, monthly or annually or between about 1 to 10 weeks, or for as long as appropriate, for example, to achieve a reduction in the onset, progression, severity, frequency, duration of one or more symptoms or complications associated with or caused by cancer or an infection, immune disorder, or autoimmune response, disorder or disease, or an adverse symptom, condition or complication associated with or caused by cancer or an infection, immune disorder, or autoimmune response, disorder or disease. Thus, a method can be practiced one or more times (e.g., 1-10, 1-5 or 1-3 times) an hour, day, week, month, or year. The skilled artisan will know when it is appropriate to delay or discontinue administration. A non-limiting dosage schedule is 1-7 times per week, for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more weeks, and any numerical value or range or value within such ranges.

[0080] The term “contacting” means direct or indirect binding or interaction between two or more. A particular example of direct interaction is binding. A particular example of an indirect interaction is where one entity acts upon an intermediary molecule, which in turn acts upon the second referenced entity. Contacting as used herein includes in solution, in solid phase, in vitro, ex vivo, in a cell and in vivo. Contacting in vivo can be referred to as administering, or administration.

[0081] The term “antigen spread” (also referred to as “determinant spread” or “epitope spread”) refers to the induction and amplification of an immune response from a dominant antigen to antigens distinct from the original target (secondary antigens). Secondary antigens may be a different epitope of the first antigen, or a different antigen all together. See e.g. El- Sayes et al. (2021) Cancers (Basel). Feb; 13(4): 806, doi: 10.3390 / cancersl3040806 and Ma et al. (2023) Cell 186, 3148-3165, doi.org / 10.1016 / j.cell.2023.06.002.

[0082] CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is an acronym for DNA loci that contain multiple, short, direct repetitions of base sequences. The prokaryotic CRISPR / Cas system has been adapted for use as gene editing (silencing, enhancing or changing specific genes) for use in eukaryotes (see, for example, Cong,-17-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Science, 15:339(6121):819-823 (2013) and Jinek, et al., Science, 337(6096): 816-21 (2012)). By transfecting a cell with elements including a Cas gene and specifically designed CRISPRs, nucleic acid sequences can be cut and modified at any desired location. Methods of preparing compositions for use in genome editing using the CRISPR / Cas systems are described in detail in US Pub. No. 2016 / 0340661, US Pub. No. 20160340662, US Pub. No. 2016 / 0354487, US Pub. No. 2016 / 0355796, US Pub. No. 20160355797, and WO 2014 / 018423, which are specifically incorporated by reference herein in their entireties.

[0083] Thus, as used herein, “CRISPR system” refers collectively to transcripts and other elements involved in the expression of or directing the activity of CRISPR-associated (“Cas”) genes, including sequences encoding a Cas gene, a tracr (trans-activating CRISPR) sequence (e.g., tracrRNA or an active partial tracrRNA), a tracr-mate sequence (encompassing a “direct repeat” and a tracrRNA-processed partial direct repeat in the context of an endogenous CRISPR system), a guide sequence (also referred to as a “spacer”, “guide RNA” or “gRNA” in the context of an endogenous CRISPR system), or other sequences and transcripts from a CRISPR locus. One or more tracr mate sequences operably linked to a guide sequence (e.g., direct repeat-spacer-direct repeat) can also be referred to as “pre-crRNA” (pre-CRISPR RNA) before processing or crRNA after processing by a nuclease.

[0084] In some embodiments, one or more vectors driving expression of one or more elements of a CRISPR system are introduced into a target cell such that expression of the elements of the CRISPR system direct formation of a CRISPR complex at one or more target sites. While the specifics can be varied in different engineered CRISPR systems, the overall methodology is similar. A practitioner interested in using CRISPR technology to target a DNA sequence can insert a short DNA fragment containing the target sequence into a guide RNA expression plasmid. The sgRNA expression plasmid contains the target sequence (about 20 nucleotides), a form of the tracrRNA sequence (the scaffold) as well as a suitable promoter and necessary elements for proper processing in eukaryotic cells. Such vectors are commercially available (see, for example, Addgene). Many of the systems rely on custom, complementary oligos that are annealed to form a double stranded DNA and then cloned into the sgRNA expression plasmid. Co-expression of the sgRNA and the appropriate Cas enzyme-18-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 from the same or separate plasmids in transfected cells results in a single or double strand break (depending of the activity of the Cas enzyme) at the desired target site.Compositions, Subject Population and Methods of Administration

[0085] As used herein “patient” and “subject” are used interchangeably.

[0086] In the methods described herein, the term “subject” refers includes but is not limited to a subject at risk of an immune disorder, or autoimmune response, disorder or disease, as well as a subject that has already developed an immune disorder, or autoimmune response, disorder or disease. Such subjects, include mammalian animals (mammals), such as a nonhuman primate (apes, gibbons, gorillas, chimpanzees, orangutans, macaques), a domestic animal (dogs and cats), a farm animal (poultry such as chickens and ducks, horses, cows, goats, sheep, pigs), experimental animal (mouse, rat, rabbit, guinea pig) and humans. Subjects include animal disease models, for example, mouse and other animal models of immune disorders, or autoimmune response, disorder or disease known in the art.

[0087] In some embodiments in the methods described herein, the subject is an adult human. In other embodiments the subject is a juvenile human.

[0088] In the methods described herein, administering a T-cell comprising a mutation, and / or composition can be accomplished by any method known in the art suitable for the particular type of agonist and formulation selected. Suitable routes of administration include without Limitation oral, intratumoral, parenteral (including intramuscular, subcutaneous, intradermal, intravascular, intravenous, intraarterial, intraarticular intramedullar}' and intrathecal), intraperitoneal, and topical (including dermal / epicutaneous, transdermal, mucosal, transmucosal, intranasal (e.g., by nasal spray or drop), intraocular (e.g., by eye drop), pulmonary (e.g., by inhalation), buccal, sublingual, rectal and vaginal).

[0089] In some aspects, in the methods described herein, the administering to a subject in need can be done intravenously or subcutaneously. In other aspects, in the methods described herein, the administering to a subject in need can be topical.-19-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0090] In some aspects of the methods described herein, an additional therapeutic agent is administered to the subject in need. In one embodiment, the additional therapeutic agent is a chemotherapeutic agent.

[0091] Doses in the methods described herein can be based upon current existing protocols, empirically determined, using animal disease models or optionally in human clinical trials. Initial study doses can be based upon animal studies, e.g. a mouse, and the amount treatment or agent disclosed herein administered in an amount that is determined to be effective. Exemplary non-limiting amounts (doses) are in a range of about 0.1 mg / kg to about 100 mg / kg, and any numerical value or range or value within such ranges. Greater or lesser amounts (doses) can be administered, for example, 0.01-500 mg / kg, and any numerical value or range or value within such ranges. The dose can be adjusted according to the mass of a subject, and will generally be in a range from about 1-10 ug / kg, 10-25 ug / kg, 25-50 ug / kg, 50-100 ug / kg, 100-500 ug / kg, 500-1,000 ug / kg, 1-5 mg / kg, 5-10 mg / kg, 10-20 mg / kg, 20-50 mg / kg, 50-100 mg / kg, 100-250 mg / kg, 250-500 mg / kg, or more, two, three, four, or more times per hour, day, week, month or annually. A typical range will be from about 0.3 mg / kg to about 50 mg / kg, 0-25 mg / kg, or 1.0-10 mg / kg, or any numerical value or range or value within such ranges.

[0092] The maximum tolerable dose of the methods described herein can be readily established, and the effective amount providing a detectable therapeutic benefit to a patient may also be determined, as can the temporal requirements for administering each agent to provide a detectable therapeutic benefit to the patient. Accordingly, while certain dose and administration regimens are exemplified herein, these examples in no way limit the dose and administration regimen that may be provided to a patient in practicing the present disclosure.

[0093] Doses can vary and depend upon whether the treatment is prophylactic or therapeutic, whether a subject has previously had cancer or an infection, immune disorder, or autoimmune response, disorder or disease, the onset, progression, severity, frequency, duration probability of or susceptibility of the symptom, condition, pathology or complication, the treatment protocol and compositions, the clinical endpoint desired, the occurrence of previous or simultaneous treatments, the general health, age, gender, race or immunological competency of the subject and other factors that will be appreciated by the skilled artisan. The skilled-20-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 artisan will appreciate the factors that may influence the dosage and timing required to provide an amount sufficient for providing a therapeutic or prophylactic benefit.(0094] In the methods described herein, the route, dose, number and frequency of administrations, treatments, and timing / intervals between treatment and disease development can be modified. In certain embodiments, a desirable treatment of the present disclosure will elicit robust, long-lasting immunity against cancer or an infection, immune disorder, or autoimmune response, disorder or disease. Thus, in certain embodiments, disclosure methods, uses and compositions provide long-lasting immunity to cancer or an infection, immune disorder, or autoimmune response, disorder or disease.

[0095] As used herein the term “pharmaceutically acceptable” and “physiologically acceptable” mean a biologically acceptable formulation, gaseous, liquid or solid, or mixture thereof, which is suitable for one or more routes of administration, in vivo delivery or contact. Such formulations include solvents (aqueous or non-aqueous), solutions (aqueous or non-aqueous), emulsions (e.g., oil-in-water or water-in-oil), suspensions, syrups, elixirs, dispersion and suspension media, coatings, isotonic and absorption promoting or delaying agents, compatible with pharmaceutical administration or in vivo contact or delivery.Aqueous and non-aqueous solvents, solutions and suspensions may include suspending agents and thickening agents. Such pharmaceutically acceptable carriers include tablets (coated or uncoated), capsules (hard or soft), microbeads, powder, granules and crystals. Supplementary active compounds (e.g., preservatives, antibacterial, antiviral and antifungal agents) can also be incorporated into the compositions.

[0096] Compositions (i.e. pharmaceutical compositions) described herein can be formulated to be compatible with a particular route of administration. Thus, pharmaceutical compositions include carriers, diluents, or excipients suitable for administration by various routes.Exemplary routes of administration for contact or in vivo delivery which a composition can optionally be formulated include inhalation, respiration, intranasal, intubation, intrapulmonary instillation, oral, buccal, intrapulmonary, intradermal, topical, dermal, parenteral, sublingual, subcutaneous, intravascular, intrathecal, intraarticular, intracavity, transdermal, iontophoretic, intraocular, opthalmic, optical, intravenous (i.v.), intramuscular, intraglandular, intraorgan, or intralymphatic.-21-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0097] Formulations suitable for parenteral administration comprise aqueous and nonaqueous solutions, suspensions or emulsions of the active compound, which preparations are typically sterile and can be isotonic with the blood of the intended recipient. Non-limiting illustrative examples include water, saline, dextrose, fructose, ethanol, animal, vegetable or synthetic oils.Modes for Carrying out the Disclosure

[0098] Polynucleotide, Vectors, Cells, and Compositions thereof

[0099] According to one embodiment, described herein is a vector comprising a nucleic acid sequence encoding a polypeptide, the polypeptide comprising at least one B cell lymphoma protein mutation or functional fragment thereof. In some aspects, the polypeptide comprises at least one selected from a BCL10, CTSS, ShAPI2-MALTl, API2-MALT1 HNRNPD, FOXO1, MEF2C, HIST1H1E, IRF8, HRAS, MEF2B, BTK, IKBKB, BCL2, CARD11, MYD88, KLF2, MYC, IGH, PIK3CD, PIM2, MAP2K1, OSBPLIO, FOXP1, TNRFSF14, CD79B, HIST1H2BC, STAT6, SGK1, RRAGC, EGR1, BTG1, DIS3, ETNK1, ETS1, EZH2, HIST1H1D, IKZF3, IRF4, KLHL6, MAP2K2, mCXCR4, mIL4R, NKAP, PIM1, PPP4C, RFTN1, SOCS1, TBL1XR1, TLR2, USP8, ZBTB7A, or ZFP36L1 mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein.

[0100] In one aspect, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-33.

[0101] In some aspects, the variant is a point mutation, a gene fusion, a substitution, a gain- of-function mutation, a stop-gain mutation, an insertion mutation, a deletion mutation, a duplication mutation or a translocation.

[0102] Also described herein is a vector comprising a nucleic acid sequence encoding a polypeptide comprising a B cell lymphoma wild-type protein or functional fragment thereof. In some aspects, the polypeptide comprises a BCL2, CXCR4, mPDCDl, MYD88, RRAGC, TBL1XR1, tCD19, tCD20, MYC, FOXP1, or XPO1 wild-type protein.-22-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0103] In some aspects, the vector is a plasmid, a herpes simplex virus, a retrovirus, an adenovirus, a murine stem cell virus (MSCV), or an adeno-associated virus. In one aspect, the retrovirus is a lentivirus.

[0104] According to another embodiment, described herein is an engineered cell comprising a nucleic acid sequence encoding a polypeptide comprising at least one B cell lymphoma protein mutation or functional fragment thereof. In some aspects, the polypeptide comprises at least one selected from a BCL10, CTSS, ShAPI2-MALTl, API2-MALT1 HNRNPD, FOXO1, MEF2C, HIST1H1E, IRF8, HRAS, MEF2B, BTK, IKBKB, BCL2, CARD11, MYD88, KLF2, MYC, IGH, PIK3CD, PIM2, MAP2K1, OSBPLIO, FOXP1, TNRFSF14, CD79B, HIST1H2BC, STAT6, SGK1, RRAGC, EGR1, BTG1, DIS3, ETNK1, ETS1, EZH2, HIST1H1D, IKZF3, IRF4, KLHL6, MAP2K2, mCXCR4, mIL4R, NKAP, PIM1, PPP4C, RFTN1, SOCS1, TBL1XR1, TLR2, USP8, ZBTB7A, or ZFP36L1 mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein. In some aspects, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-33.

[0105] In some aspects, the variant is a point mutation, a gene fusion, a substitution, a gain- of-function mutation, a stop-gain mutation, an insertion mutation, a deletion mutation, a duplication mutation or a translocation.

[0106] Also described herein is an engineered cell comprising a nucleic acid sequence encoding a polypeptide comprising a B cell lymphoma wild-type protein or functional fragment thereof. In some aspects, the polypeptide comprises a BCL2, CXCR4, mPDCDl, MYD88, RRAGC, TBL1XR1, tCD19, tCD20, MYC, FOXP1, or XPO1 wild-type protein.

[0107] According to another embodiment, described herein is an engineered cell comprising a polypeptide comprising at least one B cell lymphoma protein mutation or functional fragment thereof. In some aspects, the polypeptide comprises at least one selected from a BCL10, CTSS, ShAPI2-MALTl, API2-MALT1 HNRNPD, FOXO1, MEF2C, HIST1H1E, IRF8, HRAS, MEF2B, BTK, IKBKB, BCL2, CARD11, MYD88, KLF2, MYC, IGH, PIK3CD, PIM2, MAP2K1, OSBPLIO, FOXP1, TNRFSF14, CD79B, HIST1H2BC, STAT6,-23-4919-8127-7289.1Atty. Dkt. No.: 121384-0284SGK1, RRAGC, EGR1, BTG1, DIS3, ETNK1, ETS1, EZH2, HIST1H1D, IKZF3, IRF4, KLHL6, MAP2K2, mCXCR4, mIL4R, NKAP, PIM1, PPP4C, RFTN1, S0CS1, TBL1XR1, TLR2, USP8, ZBTB7A, or ZFP36L1 mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein.

[0108] In some aspects, the variant is a point mutation, a gene fusion, a substitution, a gain- of-function mutation, a stop-gain mutation, an insertion mutation, a deletion mutation, a duplication mutation or a translocation.

[0109] Also described herein is an engineered cell comprising a polypeptide comprising a B cell lymphoma wild-type protein or functional fragment thereof. In some aspects, the polypeptide comprises BCL2, CXCR4, mPDCDl, MYD88, RRAGC, TBL1XR1, tCD19, tCD20, MYC, FOXP1, or XPO1 wild-type protein.

[0110] According to one embodiment, the engineered cell comprises the vectors described herein.

[0111] In some aspects, the engineered cell is a T cell. The T cell can be selected from a CAR T cell, CD3+ cell, CD8+ cell, CD4+ cell, regulatory T cell, a gamma delta T cell (y5T), an invariant natural killer T (iNKT) cell, a mucosal associated invariant T (MAIT) cell, a macrophage, a monocyte, a natural killer (NK) cell, a tumor infiltrating lymphocyte (TIL), a cytotoxic T cell, a T helper cell, a memory T cell, a central memory T (TCM) cell, a stem memory T (TSCM) cell, a stem-cell-like memory T cell (or stem-like memory T cells), an effector memory T (TEM) cell, a TEMRA (CD45RA+) cell, an effector T cell, a Thl cell, a Th2 cell, a Th9 cell, a Th 17 cell, a Th22 cell, a Tfh (follicular helper) cell, a natural killer T (NKT) cell, a transitional memory T (TTM) cell, a terminal effector T (TTE) cell, or a naive T (TN) cell.

[0112] In one aspect, the engineered cell is a CD8 T cell, a Jurkat T cell, or a CAR T cell.

[0113] In some aspects, the T cell further comprises a receptor with specificity for a target antigen. The receptor may be a chimeric antigen receptor (CAR) with specificity for a target antigen or a T cell receptor (TCR) having specificity for a target antigen. In other aspects the target antigen is selected from CD 19, B7H3 (CD276), BCMA (CD269), ALPPL2, Claudin-24-4919-8127-7289.1Atty. Dkt. No.: 121384-028418.2, CD123, CD171, CD179a, CD20, CD213A2, CD22, CD24, CD246, CD272, CD30, CD33, CD38, CD44v6, CD46, CD71, CD97, CEA, Claudin 6(CLDN6), CLECL1, CS-1, DLL-3, EGFR, EGFRvIII, ELF2M, EpCAM, EphA2, Ephrin B2, FAP, FLT3, GCC, GD2, GD3, GM3, GPRC5D, HER2 (ERBB2 / neu), IGLL1, IL-l lRa, KIT (CD117), KLK2, LY6G6D, MUC1, NCAM, p53R175H, PAP, PDGFR-P, PRAME, PRSS21, PSCA, PSMA, R0R1, SIRPa, SSEA-4, TAG72, TEM1 / CD248, TEM7R, TSHR, VEGFR2, ALPI, citrullinated vimentin, cMet, and / or Axl. In yet other aspects the target antigen is selected from cell surface receptors, adhesion proteins, integrins, mucins, lectins, tumor-associated antigens, and tumor-specific antigens.101141 In some aspects, the engineered cell has increased or decreased signaling through the API, NF AT, KFKB, and / or PD1 pathways as compared to a cell of the same cell type without the nucleic acid or polypeptide. See FIG. 5C.

[0115] In some aspects, the engineered cell has increased or decreased cytokine production as compared to a cell of the same cell type without the nucleic acid or polypeptide. In some aspects, the cytokine is selected from IL-2, IL-4, 11-5, TNF alpha, IFN- gamma and / or IL-13. See FIGS. 5A-5B|0116] Also provided herein is a composition comprising the engineered cell. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. In some embodiments, the composition further comprises additional agents, including therapeutic drug agents.

[0117] Variants in the polypeptides, vectors, and cells(0118] According to some aspects, the B cell lymphoma wild-type protein or variant provided herein is selected from a variant in Table 1 or Table 5. In one aspect, the selected variant has higher expression in the tumor microenvironment and / or tumor draining lymph nodes than the negative control. The negative control can be a vector or engineered cell that does not comprise the wild-type protein or variant, or nucleotide encoding the wild type protein or variant.-25-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0119] According to some aspects, the protein variant or wild-type protein provided herein is selected from: a) BCL10 substitution at amino acid 58, 140, or 209; b) BCL10 fusion; c) CTSS substitution at amino acid 132; d) ShAPI2-MALTl fusion or API2-MALT1 fusion; e) HNRNPD substitution at amino acid 48; f) FOXO1 substitution at amino acid 24; g) MEF2C substitution at amino acid 389; h) HIST1H1E substitution at amino acid 158; i) IRF8 substitution at amino acid 23; j) HRAS substitution at amino acid 145; k) MEF2B substitution at amino acid 83; l) BTK substitution at amino acid 474 and 513; m) IKBKB substitution at amino acid 171; n) BCL2 substitution at amino acid 7 or 33 or BCL2 wild-type; o) CARD11 substitution at amino acid 49, 123, or 225; p) MYD88 substitution at amino acid 265; q) KLF2 substitution at amino acid 291; r) MYC-IGH / MYC fusion or MYC wild-type;-26-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 s) PIK3CD substitution at amino acid 1021; t) PIM2 substitution at amino acid 27 or 31; u) MAP2K1 substitution at amino acid 53; v) OSBPLIO substitution at amino acid 94; w) IGH-FOXP1 / FOXP1 fusion or FOXP1 wild-type; x) TNRFSF14 substitution at amino acid 135; y) CD79B substitution at amino acid 196; z) HIST1H2BC substitution at amino acid 63; aa) STAT6 substitution at amino acid 419; ab) SGK1 substitution at amino acid 143; ac) RRAGC substitution at amino acid 90 or 75, or wild-type; ad) EGR1 substitution at amino acid 34; ae) ATP6V1B2 substitution at amino acid 371 or 400; af) BTG1 substitution at amino acid 36; ag) CXCR4 wild-type; ah) DIS3 substitution at amino acid 488 ai) ETNK1 substitution at amino acid 244; aj) ETS1 substitution at amino acid 23; ak) EZH2 substitution at amino acid 113 or 646; al) HIST1H1D substitution at amino acid 186;-27-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 am) IKZF3 substitution at amino acid 162; an) IRF4 substitution at amino acid 66; ao) KLHL6 substitution at amino acid 90; ap) MAP2K2 substitution at amino acid 60; aq) mCXCR4 substitution at amino acid 345; ar) mIL4R substitution at amino acid 243; as) mPDCDl wild-type; at) MYD88 wild-type; au) NKAP substitution at amino acid 405; av) PIM1 substitution at amino acid 81; aw) PIM2 substitution at amino acid 31; ax) PPP4C substitution at amino acid 54; ay) PTPN 11 wild-type; az) RFTN1 substitution at amino acid 255; ba) SOCS1 substitution at amino acid 17; bb) TBL1XR1 substitution at amino acid 446 or wild-type; be) tCD19 wild-type; bd) tCD20 wild-type; be) TLR2 substitution at amino acid 327; bf) USP8 substitution at amino acid 657;-28-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 bg) XP01 wild-type; bh) ZBTB7A substitution at amino acid 247; and / or bi) ZFP36L1 substitution at amino acid 19.

[0120] According to some aspects, the protein is encoded by a nucleotide selected from the sequences of SEQ ID NOs: 1-70, 79-81. According to some aspects, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-70, 79-81.

[0121] According to some aspects, the protein a variant of a wild type protein.

[0122] According to one aspect, the variant is naturally occurring. According to another aspect, the variant is non-naturally occurring.|0123] BCL10

[0124] As used herein, BCL10 refers to the B-cell lymphoma / leukemia 10 protein and is encoded by the BCL10 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under UNIPROT 095999, NCBI NP_003912.1, or NCBI NG_012216.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type BCL10 has a sequence according to accession number according to NP 003912.1, which is 233 amino acids in length.

[0125] In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1 and encodes a BCL10 polypeptide with a R58Q substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2 and encodes a BCL10 polypeptide with a E140X substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%,-29-4919-8127-7289.1Atty. Dkt. No.: 121384-028483%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3 and encodes a BCL10 polypeptide with a L209X substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 4 and encodes a BCL10 wild-type. In one embodiment, the substitution is a R58Q+E140X double substitution.

[0126] In one embodiment, the polypeptide is BCL10 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to NP 003912.1. In one embodiment, the polypeptide is BCL10 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to NP 003912.1 and includes a substitution at amino acid 58, wherein amino acid 58 is determined using the full length sequence according to NP 003912.1. In one embodiment the substitution is a R58Q substitution. In some embodiments, the polypeptide is BCL10 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to NP 003912.1 and includes a substitution at amino acid 140, wherein amino acid 140 is determined using the full length sequence according to NP 003912.1. In one embodiment the substitution is a E140X substitution. In some embodiments, the polypeptide is BCL10 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to NP 003912.1 and includes a substitution at amino acid 209, wherein amino acid 209 is determined using the full length sequence according to NP 003912.1. In one embodiment the substitution is a L209X substitution.-30-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0127] In some embodiments, the nucleic acid sequence encodes an BCL10 fusion polypeptide. In some embodiments, the nucleic acid of SEQ ID NO: 4 is fused to form a BCL10 fusion.

[0128] CTSS

[0129] As used herein, CTSS refers to the cathepsin S protein and is encoded by the CTSS gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 001186668.1, or NCBI NM_001199739.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype CTSS has a sequence according to accession number according to ENST00000368985.7, which is 331 amino acids in length. ENST00000368985.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 5 and encodes a CTSS polypeptide with a Y132D substitution. In some embodiments, the polypeptide is CTSS having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000368985.7 and includes a substitution at amino acid 132, wherein amino acid 132 is determined using the full length sequence according to ENST00000368985.7. In one embodiment the substitution is a Y132D substitution.

[0130] API2[01311 As used herein, API2, which is also known as BIRC3, refers to the baculoviral IAP repeat-containing protein 3 protein and is encoded by the API2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP_001156.1 or NCBI NG_065365.1, each of which is incorporated by reference herein in its entirety.

[0132] MALT1-31-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0133] As used herein, MALT1, refers to the mucosa-associated lymphoid tissue lymphoma translocation protein 1 protein and is encoded by the MALT1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_033893.2 or NP_006776.1, each of which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 6 and encodes a API2-MALT1 polypeptide with a API2-MALT1 fusion. In one embodiment, the polypeptide is a API2-MALT1 fusion having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 71.(0134] shAPI2 is a shortened isoform of the API2 protein. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 80 and encodes a shAPI2- MALT1 polypeptide with a shAPI2-MALTl fusion. In one embodiment, the polypeptide is a shAPI2-MALTl fusion having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 82.

[0135] HNRNPD

[0136] As used herein, HNRNPD, refers to the heterogeneous nuclear ribonucleoprotein DO protein and is encoded by the HNRNPD gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_029103.1 or NP_001003810.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type HNRNPD has a sequence according to accession number according to ENST00000313899.11, which is 355 amino acids in length. ENST00000313899.11 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,-32-4919-8127-7289.1Atty. Dkt. No.: 121384-028495%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 7 and encodes a HNRNPD polypeptide with a G48R substitution. In some embodiments, the polypeptide is HNRNPD having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000313899.11 and includes a substitution at amino acid 48, wherein amino acid 48 is determined using the full length sequence according to ENST00000313899.11. In one embodiment the substitution is a G48R substitution.

[0137] FOXO1

[0138] As used herein, FOXO1, refers to the forkhead box protein 01 protein and is encoded by the FOXO1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 002006.2 or NG_023244.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type FOXO1 has a sequence according to accession number according to ENST00000379561.5, which is 655 amino acids in length.ENST00000379561.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 8 and encodes a FOXO1 polypeptide including a substitution at amino acid 24 with a T24I substitution. In some embodiments, the polypeptide is FOXO1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000379561.5 and includes a substitution at amino acid 48, wherein amino acid 24 is determined using the full length sequence according to ENST00000379561.5. In one embodiment the substitution is a T24I substitution.

[0139] MEF2C

[0140] As used herein, MEF2C, refers to the myocyte-specific enhancer factor 2C protein and is encoded by the MEF2C gene or a fragment thereof. Non-limiting exemplary-33-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_023427.1 or NCBI NP_001124477.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type MEF2C has a sequence according to accession number according to ENST00000636294.1, which is 474 amino acids in length. ENST00000636294.1 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 and encodes a MEF2C polypeptide with a N389S substitution. In some embodiments, the polypeptide is MEF2C having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000636294.1 and includes a substitution at amino acid 389, wherein amino acid 389 is determined using the full length sequence according to ENST00000636294.1. In one embodiment the substitution is a N389S substitution.

[0141] HIST1H1E

[0142] As used herein, HIST1H1E, also known as Hl-4, refers to the histone Hl.4 or histone cluster 1 Hl family member e protein and is encoded by the HIST1H1E gene or a fragment thereof. A non-limiting exemplary sequence of this protein or the underlying gene or functions thereof may be found under NCBI NP 005312.1, which is incorporated by reference herein in its entirety. In some embodiments, the wild-type HIST1H1E has a sequence according to accession number according to ENST00000304218.5, which is 219 amino acids in length. ENST00000304218.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 10 and encodes a HIST1H1E polypeptide with a A158T substitution. In some embodiments, the polypeptide is HIST1H1E having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino-34-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 acid sequence according to ENST00000304218.5 and includes a substitution at amino acid 158, wherein amino acid 158 is determined using the full length sequence according to ENST00000304218.5. In one embodiment the substitution is a A158T substitution.

[0143] IRF8

[0144] As used herein, IRF8, refers to the interferon regulatory factor 8 protein and is encoded by the IRF8 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBING_029333.1 or NCBI KAI2580014.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type IRF8 has a sequence according to accession number according to KAI2580014.1, which is 126 amino acids in length. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11 and encodes a IRF8 polypeptide with a Y23H substitution. In some embodiments, the polypeptide is IRF8 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to KAI2580014.1 and includes a substitution at amino acid 23, wherein amino acid 23 is determined using the full length sequence according to KAI2580014.1. In one embodiment the substitution is a Y23H substitution.

[0145] HRAS

[0146] As used herein, HRAS, refers to the GTPase HRAS protein, also referred to as Ha- Rasl proto-oncoprotein and is encoded by the HRAS gene or a fragment thereof. Nonlimiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_007666.1 or NP_001123914.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type HRAS has a sequence according to accession number according to ENST00000451590.5, which is 189 amino acids in length. ENST00000451590.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%,-35-4919-8127-7289.1Atty. Dkt. No.: 121384-028476%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 12 and encodes a HRAS polypeptide with a S145L substitution. In some embodiments, the polypeptide is HRAS having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000451590.5and includes a substitution at amino acid 145, wherein amino acid 145 is determined using the full length sequence according to ENST00000451590.5. In one embodiment the substitution is a S145L substitution.|0147| MEF2B10148 ] As used herein, MEF2B, refers to the myocyte-specific enhancer factor 2B protein and is encoded by the MEF2B gene or a fragment thereof. Non-limiting exemplary sequence of this protein or the underlying gene or functions thereof may be found under NCBI NP_001139257.1 or NC_000019.10 Reference GRCh38.pl4 Primary Assembly (range 19145567..19170263, complement), each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type MEF2B has a sequence according to accession number according to ENST00000409224.5, which is 297 amino acids in length. ENST00000409224.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 and encodes a MEF2B polypeptide with a D83 V substitution. In some embodiments, the polypeptide is MEF2B having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000409224.5 and includes a substitution at amino acid 83, wherein amino acid 83 is determined using the full length sequence according to ENST00000409224.5. In one embodiment the substitution is a D83 V substitution.

[0149] BTK-36-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0150] As used herein, BTK, refers to the tyrosine-protein kinase BTK protein and is encoded by the BTK gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 009616.1 or NCBI NP_000052.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type BTK has a sequence according to accession number according to ENST00000308731.7, which is 659 amino acids in length.ENST00000308731.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 14 and encodes a BTK polypeptide with a T474M+E513G substitution. In some embodiments, the polypeptide is BTK having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000308731.7 and includes a substitution at amino acid 474 and 513, wherein amino acid 474 and 513 is determined using the full length sequence according to ENST00000308731.7. In one embodiment the substitution is a T474M+E513G substitution.

[0151] IKBKB

[0152] As used herein, IKBKB, refers to the inhibitor of nuclear factor kappa-B kinase subunit beta protein and is encoded by the IKBKB gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_041793.1, AAH06231.1, or NP_001177649.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type IKBKB has a sequence according to accession number according to AAH06231.1, which is 256 amino acids in length. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15 and encodes a IKBKB polypeptide with a K171T substitution. In some embodiments, the polypeptide is IKBKB having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,-37-4919-8127-7289.1Atty. Dkt. No.: 121384-028488%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to according to AAH06231.1 and includes a substitution at amino acid 171, wherein amino acid 171 is determined using the full length sequence according to AAH06231.1. In one embodiment the substitution is a K171T substitution.|0153] BCL210154] As used herein, BCL2, refers to the apoptosis regulator Bcl-2 protein and is encoded by the BCL2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 009361.1 or NP_000624.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type BCL2 has a sequence according to accession number according to ENST00000333681.4, which is 239 amino acids in length. ENST00000333681.4 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 16 and encodes a BCL2 polypeptide with a T7I substitution. In some embodiments, the polypeptide is BCL2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000333681.4 and includes a substitution at amino acid 7 wherein amino acid 7 is determined using the full length sequence according to ENST00000333681.4. In one embodiment the substitution is a T7I substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17 and encodes a BCL2 polypeptide with a G33R substitution. In some embodiments, the polypeptide is BCL2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000333681.4 and includes a substitution at amino acid 33 wherein amino acid 33 is determined using the full length sequence according to ENST00000333681.4. In one embodiment the substitution-38-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 is a T7I substitution. In one embodiment the substitution is a G33R substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 36 and encodes a wild-type BCL2 polypeptide. In some embodiments, the polypeptide is BCL2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000333681.4.

[0155] CARPI 1

[0156] As used herein, CARD11, refers to the caspase recruitment domain-containing protein 11 protein and is encoded by the CARD 11 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_027759.1 or NP_001311210.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type CARD 11 has a sequence according to accession number ENST00000396946.8, which is 1154 amino acids in length. ENST00000396946.8 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 18 and encodes a CARD 11 polypeptide with a C49Y substitution. In some embodiments, the polypeptide is CARD1 1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000396946.8 and includes a substitution at amino acid 49 wherein amino acid 49 is determined using the full length sequence according to ENST00000396946.8. In one embodiment the substitution is a C49Y substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 38 and encodes a CARD 11 polypeptide with a L225LI insertion. In some embodiments, the polypeptide is CARD 11 having an amino acid sequence having at least a-39-4919-8127-7289.1Atty. Dkt. No.: 121384-028475%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000396946.8 and includes an substitution at amino acid 225 wherein amino acid 225 is determined using the full length sequence according to ENST00000396946.8. In one embodiment the substitution is a L225LI insertion. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 39 and encodes a CARD 11 polypeptide with a G123S substitution. In some embodiments, the polypeptide is CARD11 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000396946.8 and includes a substitution at amino acid 123 wherein amino acid 123 is determined using the full length sequence according to ENST00000396946.8. In one embodiment the substitution is a G123S substitution.

[0157] MYD88

[0158] As used herein, MYD88, refers to myeloid differentiation primary response protein MyD88 and is encoded by the MYD88 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 016964.1, EAW64521.1, or NP_001166037.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type MYD88 has a sequence according to accession number EAW64521.1, which is 309 amino acids in length. ENST00000396334.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 54 and encodes a wild-type MYD88 polypeptide. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 19 and encodes a MYD88 polypeptide with a L265P-40-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 substitution. In some embodiments, the polypeptide is MYD88 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to EAW64521.1. In some embodiments, the polypeptide is MYD88 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to EAW64521.1 and includes a substitution at amino acid 265 wherein amino acid 265 is determined using the full length sequence according to EAW64521.1. In one embodiment the substitution is a L265P substitution.[0159| KLF2

[0160] As used herein, KLF2, refers to the Krueppel-like factor 2 protein and is encoded by the KLF2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein may be found under NCBI NP_057354.1, which is incorporated by reference herein in its entirety. In some embodiments, the wild-type KLF2 has a sequence according to accession number ENST00000248071.5, which is 355 amino acids in length. ENST00000248071.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 20 and encodes a KLF2 polypeptide with a A291T substitution. In some embodiments, the polypeptide is KLF2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000248071.5 and includes a substitution at amino acid 291 wherein amino acid 291 is determined using the full length sequence according to ENST00000248071.5 . In one embodiment the substitution is a A291T substitution.

[0161] MYC

[0162] As used herein, MYC, refers to the myc proto-oncogene protein and is encoded by the MYC gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the-41-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 underlying gene or functions thereof may be found under NCBI NG 007161.2 or NP_001341799.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type MYC has a sequence according to accession number ENST00000621592.8, which is 454 amino acids in length. ENST00000621592.8 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 21 and encodes a MYC wild-type polypeptide. In one embodiment, the polypeptide is a MYC wild-type having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 72.

[0163] IGH

[0164] As used herein, IGH, refers to the immunoglobulin heavy locus and is encoded by the IGH locus or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or locus or functions thereof may be found under NCBI NG 001019.6 or AAH73766.1, each of which is incorporated by reference herein in its entirety.

[0165] In some embodiments, the nucleic acid sequence encodes a MYC-IGH fusion polypeptide. In some embodiments, the nucleic acid of SEQ ID NO: 21 is fused to the IGH gene locus or a fragment thereof to form an MYC-IGH fusion.

[0166] PIK3CD

[0167] As used herein, PIK3CD, refers to phosphatidylinositol 4, 5 -bisphosphate 3-kinase catalytic subunit delta isoform and is encoded by the PIK3CD gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_023434.1 or NP_001337163.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type PIK3CD has a sequence according to accession number ENST00000377346.8, which is 1044 amino acids in length. ENST00000377346.8 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%,-42-4919-8127-7289.1Atty. Dkt. No.: 121384-028476%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 22 and encodes a PIK3CD polypeptide with a E1021K substitution. In some embodiments, the polypeptide is PIK3CD having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000377346.8 and includes a substitution at amino acid 1021 wherein amino acid 1021 is determined using the full length sequence according to ENST00000377346.8. In one embodiment the substitution is a E1021K substitution.|0168| PIM2101 91 As used herein, PIM2, refers to the serine / threonine-protein kinase pim-2 protein and is encoded by the PIM2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_016262.2 or NP_006866.2 ,each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type PIM2 has a sequence according to accession number ENST00000376509.4, which is 311 amino acids in length. ENST00000376509.4 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 23 and encodes a PIM2 polypeptide with a A27V substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 57 and encodes a PIM2 polypeptide with a E31D substitution. In some embodiments, the polypeptide is PIM2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000376509.4 and includes a substitution at amino acid 27 or 31 wherein amino acid 27 or 31 is determined using the full length sequence according to ENST00000376509.4. In-43-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 one embodiment the substitution is a A27V substitution. In one embodiment the substitution is a E3 ID substitution.

[0170] MAP2K1

[0171] As used herein, MAP2K1, refers to the dual specificity mitogen-activated protein kinase kinase 1 protein and is encoded by the MAP2K1 gene or a fragment thereof. Nonlimiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_008305.1 or NP_001397994.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type PIM2 has a sequence according to accession number ENST00000307102.9, which is 393 amino acids in length. ENST00000307102.9 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 24 and encodes a MAP2K1 polypeptide with a F53Y substitution. In some embodiments, the polypeptide is MAP2K1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000307102.9 and includes a substitution at amino acid 53 wherein amino acid 53 is determined using the full length sequence according to ENST00000307102.9. In one embodiment the substitution is a F53Y substitution.

[0172] OSBPLIO

[0173] As used herein, OSBPLIO, refers to oxysterol -binding protein-related protein 10 and is encoded by the OSBPLIO gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP 001167531.1, which is incorporated by reference herein in its entirety. In some embodiments, the wild-type OSBPLIO has a sequence according to accession number ENST00000396556.6, which is 764 amino acids in length. ENST00000396556.6 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,-44-4919-8127-7289.1Atty. Dkt. No.: 121384-028492%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 and encodes a OSBPLIO polypeptide with a R94K substitution. In some embodiments, the polypeptide is OSBPLIO having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000396556.6 and includes a substitution at amino acid 94 wherein amino acid 94 is determined using the full length sequence according to ENST00000396556.6. In one embodiment the substitution is a R94K substitution.

[0174] FOXP1

[0175] As used herein, FOXP1, refers to forkhead box protein Pl and is encoded by the FOXP1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_028243.1 or NP_001012523.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type FOXP1 has a sequence according to accession number ENST00000615603.4. ENST00000615603.4is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 26 and encodes a FOXP1 wild-type polypeptide. In one embodiment, the polypeptide is a FOXP1 wild-type having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 78.

[0176] In some embodiments, the nucleic acid sequence encodes an IGH-FOXP1 fusion polypeptide. In some embodiments, the nucleic acid of SEQ ID NO: 26 is fused to the IGH gene locus or a fragment thereof to form an IGH-FOXP1 fusion.

[0177] TNFRSF14

[0178] As used herein, TNFRSF14, refers to tumor necrosis factor receptor superfamily member 14 and is encoded by the TNFRSF14 gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under UniProtKB Q92956, which is-45-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 incorporated by reference herein in its entirety. In some embodiments, the wild-type TNFRSF14 has a sequence according to accession number ENST00000409119.5, which is 193 amino acids in length. ENST00000409119.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27 and encodes a TNFRSF14 polypeptide with a C135S substitution. In some embodiments, the polypeptide is TNFRSF14 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000409119.5 and includes a substitution at amino acid 135 wherein amino acid 135 is determined using the full length sequence according to ENST00000409119.5. In one embodiment the substitution is a C135S substitution.|0179] CD79B

[0180] As used herein, CD79B, refers to B-cell antigen receptor complex-associated protein beta chain and is encoded by the CD79B gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_007368.1 or NP_000617.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type CD79B has a sequence according to accession number ENST00000006750.7, which is 229 amino acids in length.ENST00000006750.7is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 28 and encodes a CD79B polypeptide with a Y196F substitution. In some embodiments, the polypeptide is CD79B having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000006750.7 and includes a substitution at amino acid 196 wherein amino acid 196 is determined using the full length-46-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 sequence according to ENST00000006750.7. In one embodiment the substitution is a Y196F substitution.(0181) HIST1H2BC

[0182] As used herein, HIST1H2BC, refers to histone cluster 1, H2bc and is encoded by the HIST1H2BC gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP_001395693.1, which is incorporated by reference herein in its entirety. In some embodiments, the wild-type HIST1H2BC has a sequence according to accession number ENST00000396984.1, which is 126 amino acids in length.ENST00000396984.1 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 29 and encodes a HIST1H2BC polypeptide with a M63I substitution. In some embodiments, the polypeptide is HIST1H2BC having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000396984.1 and includes a substitution at amino acid 196 wherein amino acid 196 is determined using the full length sequence according to ENST00000396984.1. In one embodiment the substitution is a M63I substitution.

[0183] STAT6

[0184] As used herein, STAT6, refers to signal transducer and activator of transcription 6 and is encoded by the STAT6 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_021272.2 or NP_001171549.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type STAT6 has a sequence according to accession number ENST00000300134.7, which is 847 amino acids in length. ENST00000300134.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,-47-4919-8127-7289.1Atty. Dkt. No.: 121384-028499%, or 100% sequence identity to SEQ ID NO: 30 and encodes a STAT6 polypeptide with a D419G substitution. In some embodiments, the polypeptide is STAT6 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000300134.7 and includes a substitution at amino acid 419 wherein amino acid 419 is determined using the full length sequence according to ENST00000300134.7. In one embodiment the substitution is a D419G substitution.

[0185] SGK1

[0186] As used herein, SGK1, refers to serine / threonine-protein kinase Sgkl and is encoded by the SGK1 gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP 001137148.1, which is incorporated by reference herein in its entirety. In some embodiments, the wild-type SGK1 has a sequence according to accession number ENST00000367858.9, which is 526 amino acids in length. ENST00000367858.9 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 31 and encodes a SGK1 polypeptide with a A143V substitution. In some embodiments, the polypeptide is SGK1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000367858.9 and includes a substitution at amino acid 143 wherein amino acid 143 is determined using the full length sequence according to ENST00000367858.9. In one embodiment the substitution is a A143V substitution.

[0187] RRAGC

[0188] As used herein, RRAGC, refers to ras-related GTP -binding protein C and is encoded by the RRAGC gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP 001258780.1, which is incorporated by reference herein in its entirety. In some embodiments, the wild-type RRAGC has a sequence according to accession number ENST00000373001.3, which is 399 amino acids in length.-48-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ENST00000373001.3 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 79 and encodes a wild-type RRAGC polypeptide. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 32 and encodes a RRAGC polypeptide with a T90N substitution. In some embodiments, the polypeptide is RRAGC having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000373001.3 and includes a substitution at amino acid 90 wherein amino acid 90 is determined using the full length sequence according to ENST00000373001.3. In one embodiment the substitution is a T90N substitution. In some embodiments, the polypeptide is RRAGC having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000373001.3.

[0189] In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 81 and encodes a RRAGC polypeptide with a S75C substitution. In some embodiments, the polypeptide is RRAGC having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000373001.3 and includes a substitution at amino acid 75 wherein amino acid 75 is determined using the full length sequence according to ENST00000373001.3. In one embodiment the substitution is a S75C substitution.

[0190] EGR14919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0191] As used herein, EGR1, refers to early growth response protein 1 and is encoded by the EGRlgene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 021374.1 or NP 001955.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type EGR1 has a sequence according to accession number ENST00000239938.4, which is 543 amino acids in length. ENST00000239938.4 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 33 and encodes a EGR1 polypeptide with a K34N substitution. In some embodiments, the polypeptide is EGR1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000239938.4 and includes a substitution at amino acid 34 wherein amino acid 34 is determined using the full length sequence according to ENST00000239938.4. In one embodiment the substitution is a K34N substitution.[0192[ ATP6V1B2

[0193] As used herein, ATP6V1B2, refers to TPase H+ transporting VI subunit B2 and is encoded by the ATP6V1B2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_047013.1 or NP_001684.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type EGR1 has a sequence according to accession number ENST00000276390.6, which is 511 amino acids in length. ENST00000276390.6 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 34 and encodes a ATP6V1B2 polypeptide with a Y371C substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%-50-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 sequence identity to SEQ ID NO: 35 and encodes a ATP6V1B2 polypeptide with a R400Q substitution. In some embodiments, the polypeptide is ATP6V1B2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000276390.6 and includes a substitution at amino acid 371 or 400 wherein amino acid 371 or 400 is determined using the full length sequence according to ENST00000276390.6. In one embodiment the substitution is a Y371C substitution. In one embodiment the substitution is a R400Q substitution.

[0194] BTG1

[0015] As used herein, BTG1, refers to BTG anti-proliferation factor 1 and is encoded by the BTG1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 065368.1 or NP 001722.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type BTG1 has a sequence according to accession number ENST00000256015.4, which is 171 amino acids in length. ENST00000256015.4 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 37 and encodes a BTG1 polypeptide with a Q36H substitution. In some embodiments, the polypeptide is BTG1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000256015.4 and includes a substitution at amino acid 36 wherein amino acid 36 is determined using the full length sequence according to ENST00000256015.4. In one embodiment the substitution is a Q36H substitution.

[0196] CXCR4

[0197] As used herein, CXCR4, refers to C-X-C motif chemokine receptor 4 and is encoded by the CXCR4 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 011587.1 or-51-4919-8127-7289.1Atty. Dkt. No.: 121384-0284NP_OO 1008540.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type CXCR4 has a sequence according to accession number ENST00000409817.1, which is 356 amino acids in length. ENST00000409817.1 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 40 and encodes a CXCR4 polypeptide. In some embodiments, the polypeptide is MYD88 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000409817.1.(0198] mCXCR4(01 9] mCXCR4 is murinized CXCR. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 51 and encodes a mCXCR4 polypeptide with a S345X substitution. In some embodiments, the polypeptide is mCXCR4 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to sequence identity to SEQ ID NO: 73 including a substitution at amino acid 345. In one embodiment the substitution is S345X.

[0200] DIS3

[0201] As used herein, DIS3, refers to DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease and is encoded by the DIS3 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 001121698.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type DIS3 has a sequence according to accession number ENST00000545453.5, which is 797 amino acids in length. ENST00000545453.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence-52-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 41 and encodes a DIS3 polypeptide with a D488N substitution. In some embodiments, the polypeptide is DIS3 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000545453.5 and includes a substitution at amino acid 488 wherein amino acid 488 is determined using the full length sequence according to ENST00000545453.5. In one embodiment the substitution is a D488N substitution.

[0202] ETNK1102031 As used herein, ETNK1, refers to ethanolamine kinase land is encoded by the ETNK1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 065161.1 or NP_001034570.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type ETNK1 has a sequence according to accession number ENST00000266517.8, which is 363 amino acids in length. ENST00000266517.8 is incorporated by reference herein in its entirety.

[0204] In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 42 and encodes a ETNK1 polypeptide with a N244S substitution. In some embodiments, the polypeptide is ETNK1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000266517.8 and includes a substitution at amino acid 244 wherein amino acid 244 is determined using the full length sequence according to ENST00000266517.8. In one embodiment the substitution is a N244S substitution.

[0205] ETS14919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0206] As used herein, ETS1, refers to TS proto-oncogene 1, transcription factor and is encoded by the ETS1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBINP_001137292.1 or NG_029555.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type ETS1 has a sequence according to accession number ENST00000535549.5, which is 225 amino acids in length. ENST00000535549.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 43 and encodes a ETS1 polypeptide with a L23F substitution. In some embodiments, the polypeptide is ETS1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000535549.5 and includes a substitution at amino acid 23 wherein amino acid 23 is determined using the full length sequence according to ENST00000535549.5. In one embodiment the substitution is a L23F substitution.

[0207] EZH2

[0208] As used herein, EZH2, refers to enhancer of zeste 2 polycomb repressive complex 2 subunit and is encoded by the EZH2gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_032043.1 or NP_001190176.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type EGR1 has a sequence according to accession number ENST00000320356.6, which is 751 amino acids in length.ENST00000320356.6 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 44 and encodes a EZH2 polypeptide with a W113C substitution. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,-54-4919-8127-7289.1Atty. Dkt. No.: 121384-028499%, or 100% sequence identity to SEQ ID NO: 45 and encodes a EZH2 polypeptide with a Y646F substitution. In some embodiments, the polypeptide is EZH2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000320356.6 and includes a substitution at amino acid 113 or 646 wherein amino acid 113 or 646 is determined using the full length sequence according to ENST00000320356.6. In one embodiment the substitution is a W113C substitution. In one embodiment the substitution is a Y646F substitution.

[0209] HIST1H1D

[0210] As used herein, HIST1H1D, refers to Hl.3 linker histone, cluster member and is encoded by the HIST1H1D gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 005311.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type HIST1H1D has a sequence according to accession number ENST00000244534.6, which is 221 amino acids in length. ENST00000244534.6 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 46 and encodes a HIST1H1D polypeptide with a A186T substitution. In some embodiments, the polypeptide is HIST1H1D having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000244534.6 and includes a substitution at amino acid 186 wherein amino acid 186 is determined using the full length sequence according to ENST00000244534.6. In one embodiment the substitution is a A186T substitution.

[0211] IKZF3

[0212] As used herein, IKZF3, refers to IKAROS family zinc finger 3 and is encoded by the IKZF3 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the-55-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 underlying gene or functions thereof may be found under NCBI NG_029104.2 or NP_001244337.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type IKZF3 has a sequence according to accession number ENST00000346243.7, which is 431 amino acids in length. ENST00000346243.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 47 and encodes a IKZF3 polypeptide with a L162R substitution. In some embodiments, the polypeptide is IKZF3 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000346243.7 and includes a substitution at amino acid 162 wherein amino acid 162 is determined using the full length sequence according to ENST00000346243.7. In one embodiment the substitution is a L162R substitution.|0213| IRF4

[0214] As used herein, IRF4, refers to interferon regulatory factor 4 and is encoded by the IRF4 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_027728.1 or NP 001182215.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type IRF4 has a sequence according to accession number ENST00000380956.8, which is 451 amino acids in length. ENST00000380956.8 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 48 and encodes a IRF4 polypeptide with a E66K substitution. In some embodiments, the polypeptide is IRF4 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000380956.8 and includes a substitution at amino4919-8127-7289.1Atty. Dkt. No.: 121384-0284 acid 66 wherein amino acid 66 is determined using the full length sequence according to ENST00000380956.8. In one embodiment the substitution is a E66K substitution.

[0215] KLHL6

[0216] As used herein, KLHL6, refers to kelch like family member 6 and is encoded by the KLHL6 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 053012.1 or NP 569713.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type KLHL6 has a sequence according to accession number ENST00000341319.7, which is 621 amino acids in length. ENST00000341319.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 49 and encodes a KLHL6 polypeptide with a L90V substitution. In some embodiments, the polypeptide is KLHL6 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000341319.7 and includes a substitution at amino acid 90 wherein amino acid 90 is determined using the full length sequence according to ENST00000341319.7. In one embodiment the substitution is a L90V substitution.

[0217] MAP2K2

[0218] As used herein, MAP2K2, refers to mitogen-activated protein kinase kinase 2 and is encoded by the MAP2K2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_007996.1 or NP_109587.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type MAP2K2 has a sequence according to accession number ENST00000262948.9, which is 400 amino acids in length. ENST00000262948.9 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%,-57-4919-8127-7289.1Atty. Dkt. No.: 121384-028495%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 50 and encodes a MAP2K2 polypeptide with a Q60P substitution. In some embodiments, the polypeptide is MAP2K2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000262948.9 and includes a substitution at amino acid 60 wherein amino acid 60 is determined using the full length sequence according to ENST00000262948.9. In one embodiment the substitution is a Q60P substitution.

[0219] mIL4R

[0220] As used herein, IL4R, refers to interleukin 4 receptor and is encoded by the IL4R gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 012086.1 or NP 000409.1, each of which is incorporated by reference herein in its entirety. mIL4R is murinized IL4R. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 52 and encodes a mILR4 polypeptide with a L243N substitution. In some embodiments, the polypeptide is mILR4having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to sequence identity to SEQ ID NO: 74 and includes a substitution at amino acid 234. In one embodiment the substitution is a L243N substitution.

[0221] mPDCDl

[0222] As used herein, PDCD1, refers to programmed cell death land is encoded by the PDCDlgene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 012086.1 or NP 000409.1, each of which is incorporated by reference herein in its entirety. mPDCDl is murinized PDCD1. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,-58-4919-8127-7289.1Atty. Dkt. No.: 121384-028488%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 53 and encodes a mPDCDl polypeptide. In some embodiments, the polypeptide is mPDCDlhaving an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to sequence identity to SEQ ID NO: 75.

[0223] NKAP

[0224] As used herein, NKAP, refers to NFKB activating protein and is encoded by the NKAP gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 021260.1 or NP 078804.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type NKAP has a sequence according to accession number ENST00000371410.4, which is 415 amino acids in length. ENST00000371410.4 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 55 and encodes a NKAP polypeptide with a V405D substitution. In some embodiments, the polypeptide is NKAP having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000371410.4 and includes a substitution at amino acid 405 wherein amino acid 405 is determined using the full length sequence according to ENST00000371410.4. In one embodiment the substitution is a V405D substitution.(0225] PIM1

[0226] As used herein, PIM1, refers to NFKB activating protein and is encoded by the PIM1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 021260.1 or NP 078804.2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type PIM1 has a sequence according to accession number-59-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ENST00000373509.5, which is 313 amino acids in length. ENST00000373509.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 56 and encodes a PIM1 polypeptide with a P81S substitution. In some embodiments, the polypeptide is PIM1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000373509.5 and includes a substitution at amino acid 81 wherein amino acid 81 is determined using the full length sequence according to ENST00000373509.5. In one embodiment the substitution is a P81S substitution.

[0227] PPP4C

[0228] As used herein, PPP4C, refers to protein phosphatase 4 catalytic subunit and is encoded by the PPP4C gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBINP_001290432.1 2, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type PPP4C has a sequence according to accession number ENST00000279387.i l, which is 307 amino acids in length. ENST00000279387.i l is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 58 and encodes a PPP4C polypeptide with a D54N substitution. In some embodiments, the polypeptide is PPP4C having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000279387.11 and includes a substitution at amino acid 45 wherein amino acid 45 is determined using the full length sequence according to ENST00000279387.11. In one embodiment the substitution is a D54N substitution.

[0229] PTPN11-60-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0230] As used herein, PTPN11, refers to protein tyrosine phosphatase non-receptor type 11 and is encoded by the PTPN11 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_007459.1 or NP_001317366.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type PTPN11 has a sequence according to accession number ENST00000351677.6, which is 593 amino acids in length.ENST00000351677.6 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 59 and encodes a PTPN11 polypeptide. In some embodiments, the polypeptide is PTPN11 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000351677.6.|02311 RFTN1

[0232] As used herein, RFTN1, refers to raftlin, lipid raft linker 1 and is encoded by the RFTN1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 055965.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type RFTNlhas a sequence according to accession number ENST00000334133.8, which is 578 amino acids in length. ENST00000334133.8 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 60 and encodes a RFTN1 polypeptide with a S255R substitution. In some embodiments, the polypeptide is RFTNlhaving an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000334133.8 and includes a substitution at amino acid 255 wherein amino acid 255-61-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 is determined using the full length sequence according to ENST00000334133.8. In one embodiment the substitution is a S255R substitution.

[0233] SOCS1

[0234] As used herein, SOCS1, refers to suppressor of cytokine signaling 1 and is encoded by the SOCS1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 003736.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type SOCS1 has a sequence according to accession number ENST00000644787.1, which is 211 amino acids in length. ENST00000644787.1 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 61 and encodes a SOCS1 polypeptide with a A17T substitution. In some embodiments, the polypeptide is SOCS1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000644787.1 and includes a substitution at amino acid 17 wherein amino acid 17 is determined using the full length sequence according to ENST00000644787.1. In one embodiment the substitution is a A17T substitution.

[0235] TBL1XR1

[0236] As used herein, TBL1XR1, refers to TBL1X / Y related 1 and is encoded by the TBL1XR1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 047195.1 or NP 001308122.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type TBL1XR1 has a sequence according to accession number ENST00000430069.5, which is 514 amino acids in length. ENST00000430069.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,-62-4919-8127-7289.1Atty. Dkt. No.: 121384-028499%, or 100% sequence identity to SEQ ID NO: 63 and encodes a wild-type TBL1XR1 polypeptide. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 62 and encodes a TBL1XR1 polypeptide with a Y446S substitution. In some embodiments, the polypeptide is TBL1XR1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000430069.5. In some embodiments, the polypeptide is TBL1XR1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000430069.5 and includes a substitution at amino acid 17 wherein amino acid 17 is determined using the full length sequence according to ENST00000430069.5. In one embodiment the substitution is a Y446S substitution.

[0237] tCD19

[0238] As used herein, CD 19, refers to CD 19 molecule and is encoded by the CD 19 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_007275.1 or NP_001171569.1, each of which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 64 and encodes a tCD19 polypeptide. In some embodiments, the polypeptide is tCD19 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to sequence identity to SEQ ID NO: 76.

[0239] tCD20

[0240] As used herein, CD20, refers to keratin 20 and is encoded by the CD20 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene-63-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 or functions thereof may be found under NCBI NG_012286.1 or NP 061883.1, each of which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 65 and encodes a tCD20 polypeptide. In some embodiments, the polypeptide is tCD20 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to sequence identity to SEQ ID NO: 77.|0241| TLR2102421 As used herein, TLR2, refers to toll like receptor 2 is encoded by the TLR2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_016229.2 or NP_001305716.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type TLR2 has a sequence according to accession number ENST00000642700.1, which is 784 amino acids in length. ENST00000642700.1 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 66 and encodes a TLR2 polypeptide with a D327V substitution. In some embodiments, the polypeptide is TLR2 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000642700.1 and includes a substitution at amino acid 327 wherein amino acid 327 is determined using the full length sequence according to ENST00000642700.1. In one embodiment the substitution is a D327V substitution.[0243| USP8[0244| As used herein, USP8, refers to ubiquitin specific peptidase 8 is encoded by the USP8 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the-64-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 underlying gene or functions thereof may be found under NCBI NG_047101.2 orNP_001122082.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type USP8 has a sequence according to accession number ENST00000396444.7, which is 1118 amino acids in length. ENST00000396444.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 67 and encodes a USP8 polypeptide with a K657E substitution. In some embodiments, the polypeptide is USP8 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000396444.7 and includes a substitution at amino acid 657 wherein amino acid 657 is determined using the full length sequence according to ENST00000396444.7. In one embodiment the substitution is a K657E substitution.

[0245] XPO1

[0246] As used herein, XPO1, refers to exportin 1 encoded by the XPO1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 001397728.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type USP8 has a sequence according to accession number ENST00000406957.5, which is 1071 amino acids in length. ENST00000406957.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 68 and encodes a wild-type XPO1 polypeptide. In one embodiment, the polypeptide is XPO1 having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to ENST00000406957.5.

[0247] ZBTB7A-65-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0248] As used herein, ZBTB7A, refers to zinc finger and BTB domain containing 7A encoded by the ZBTB7A gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 001304919.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wild-type ZBTB7A has a sequence according to accession number ENST00000322357.8, which is 584 amino acids in length. ENST00000322357.8 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 69 and encodes a ZBTB7A polypeptide with a R247Q substitution. In some embodiments, the polypeptide is ZBTB7A having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000322357.8 and includes a substitution at amino acid 247 wherein amino acid 247 is determined using the full length sequence according to ENST00000322357.8. In one embodiment the substitution is a R247Q substitution.

[0249] ZFP36L1

[0250] As used herein, ZFP36L1, refers to ZFP36 ring finger protein like 1 encoded by the ZFP36L1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 001231627.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype ZFP36L1 has a sequence according to accession number ENST00000336440.3, which is 338 amino acids in length. ENST00000336440.3 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 70 and encodes a ZFP36L1 polypeptide with a K19N substitution. In some embodiments, the polypeptide is ZFP36L1 having an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,-66-4919-8127-7289.1Atty. Dkt. No.: 121384-028491%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity according to ENST00000336440.3 and includes a substitution at amino acid 19 wherein amino acid 19 is determined using the full length sequence according to ENST00000336440.3. In one embodiment the substitution is a K19N substitution.

[0251] Methods of Generating Vectors

[0252] According to another embodiment, described herein is a method of generating a vector. The method comprises, consists essentially of, or yet further consists of transferring a plasmid to a cell. In one aspect the plasmid comprises a nucleotide encoding a polypeptide comprising at least one B cell lymphoma protein mutant or functional fragment thereof. In some aspects, the polypeptide comprises at least one selected from a BCL10, CTSS, ShAPI2- MALT1 API2-MALT1, HNRNPD, FOXO1, MEF2C, HIST1H1E, IRF8, HRAS, MEF2B, BTK, IKBKB, BCL2, CARD11, MYD88, KLF2, MYC, IGH, PIK3CD, PIM2, MAP2K1, OSBPLIO, IGH, FOXP1, TNRFSF14, CD79B, HIST1H2BC, STAT6, SGK1, RRAGC, EGR1, BTG1, DIS3, ETNK1, ETS1, EZH2, HIST1H1D, IKZF3, IRF4, KLHL6, MAP2K2, mCXCR4, mIL4R, NKAP, PIM1, PPP4C, RFTN1, SOCS1, TBL1XR1, TLR2, USP8, ZBTB7A, or ZFP36L1 mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein.

[0253] In one aspect, the plasmid comprises a nucleotide encoding a polypeptide comprising at least one B cell lymphoma wild-type protein or functional fragment thereof. In some aspects the polypeptide comprises at a BCL2, CXCR4, mPDCDl, MYD88, RRAGC, TBL1XR1, tCD19, tCD20, or XPO1 wild-type protein.

[0254] According to some aspects, the protein is encoded by a nucleotide selected from the sequences of SEQ ID NOs: 1-70, 79-81. According to some aspects, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-70,79-81.]0255] In one aspect the vector is a retrovirus, optionally a lentivirus. In some embodiments, the retrovirus is a murine stem cell virus (MSCV).

[0256] Methods of Use-67-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0257] According to one embodiment, described herein is a method to increase the persistence of T cells in a tumor microenvironment. The method comprises, or consists essentially of, or yet further consists of contacting the tumor with the engineered T cell or composition described herein. In one aspect the tumor microenvironment is a solid tumor microenvironment. In some aspects, the contacting is in vitro or in vivo. See e.g., FIGS. 3, 9E

[0258] According to one embodiment, described herein is a method to increase the persistence of T cells in a cancer cell. The method comprises, or consists essentially of, or yet further consists of contacting the cancer cell with the engineered T cell or composition described herein. In one aspect the tumor microenvironment is a solid tumor microenvironment. In some aspects, the contacting is in vitro or in vivo.

[0259] According to another embodiment, described herein is a method to increase the persistence of T cells in a tumor microenvironment or tumor draining lymph nodes of a subject in need thereof. The method comprises, or consists essentially of, or yet further consists of administering to the subject in need the engineered T cell or composition described herein. See e.g., FIGS. 3, 4, 6, and 7.

[0260] According to yet another embodiment, described herein is a method to prevent tumor recurrence in a subject in need thereof. The method comprises, or consists essentially of, or yet further consists of administering to the subject in need the engineered cell or composition described herein after a subject has reduced tumor growth or symptoms. In some aspects, the subject is in partial or complete remission. See e.g., FIGS. 9-10

[0261] In some aspects, the cancer is a solid tumor. The cancer can be selected from small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.-68-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0262] According to another embodiment, described herein is a method to inhibit the growth of a cancer and / or increase the survival rate of a subject in need thereof. The method comprises, or consists essentially of, or yet further consists of administering to the subject in need the engineered cell or composition described herein, wherein the cancer comprises an antigen recognized by the T cell. In one aspect, the cancer is a first cancer, and growth of a second cancer is also inhibited after the administration of the engineered cell or composition. The first and second cancer can be the same or different. In some embodiments, first and / or second cancer are a tumor, optionally a solid tumor. In one aspect the second cancer is negative for the T-cell dependent antigen. See e.g., FIGS. 9-10, 13-18.

[0263] In one aspect, administration of the engineered cell or composition can prime the long term immunity of a subject in need against a cancer. See e.g., FIGS. 9-10, 15-16.

[0264] In some aspects, administration of the T-cell or composition described herein is administration is parenteral (including intramuscular, subcutaneous, intradermal, intravascular, intravenous, intraarterial, intramedullary' and intrathecal), intraperitoneal, or intra tumoral .

[0265] In some aspects, the first and / or second cancer is a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.

[0266] In some aspects, the subject in need is a mammal, optionally a human.

[0267] Kits

[0268] As set forth herein, the present disclosure provides methods for administering engineered cells and compositions to a cancer cell, tumor, or subject in need. In one aspect, the present disclosure provides kits for performing these methods as well as instructions for carrying out the methods of the present disclosure.-69-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0269] In one aspect, the kit comprises, or alternatively consists essentially of, or yet further consists of, any one or more of: a vector as disclosed herein, an engineered cell as disclosed herein, or a composition as disclosed herein, or an optional instruction of use. Such a kit may also comprise, or alternatively consist essentially of, or yet further comprise media and oter reagents appropriate for the methods disclosed herein.

[0270] The kits of this disclosure can also comprise, e.g., a buffering agent, a preservative or a protein-stabilizing agent. The kits can further comprise components necessary for detecting the detectable-label, e.g., an enzyme or a substrate. The kits can also contain a control sample or a series of control samples, which can be assayed and compared to the test sample. Each component of a kit can be enclosed within an individual container and all of the various containers can be within a single package, along with instructions for interpreting the results of the assays performed using the kit. The kits of the present disclosure may contain a written product on or in the kit container. The written product describes how to use the reagents contained in the kit.

[0271] As amenable, these suggested kit components may be packaged in a manner customary for use by those of skill in the art. For example, these suggested kit components may be provided in solution or as a liquid dispersion or the like.Experimental

[0272] Applicant has found mutations in B cell lymphoma genes that power T cell therapies. Applicant has found multiple nucleic acid sequences that when expressed by T cells in adoptive T cell therapies increase the persistence in T cells in the solid tumor microenvironment. These genes include BCL10, FOXO1, BTK, BCL2, IKBKB, and MYD88. The schematic for the in vivo solid tumor assay is seen in FIG. 8. In in vitro testing, Applicant demonstrated the mutations increase NF-kB and IL-2 in an antigen-dependent manner.

[0273] Applicant demonstrated that the nucleic acid sequences when expressed by T cells in adopt T cell therapies increased proliferation in an antigen-dependent manner. Controls in these assays were vectors expressing mCherry.-70-4919-8127-7289.1Atty. Dkt. No.: 121384-0284

[0274] For example, BCL10 mutations (FIGS. 9-14) enabled durable response with successful defense against rechallenge. MYD88 mutations (FIGS. 15-16) enabled durable response and antigen spread inducing clearance of both antigen-specific and antigen-negative tumors. IKBKB mutations (FIG. 17) also enable durable responses in cells.10275] CD8+ T cells were isolated from OT-I TCR transgenic mice. These cells were transduced with a murine stem cell virus (MSCV) retrovirus encoding the genes listed in FIG. 19 or FIG. 20. 1 million cells were transferred into mice bearing Bl 6-F 10 cells that express the cognate antigen for OT-I, ovalbumin. 7 days after transfer, the T cells were isolated and subjected to droplet-based single cell RNA-seq utilizing lOx Genomics 5’ RNA- Seq (SKU number) with cell surface antibodies (BioLegend Total Seq C proteome). The libraries were isolated, sequenced as recommended by the manufacturer. The data was processed by CellRanger 8.1.0 with modified GRCm39 as reference. The data analyzed by scanpy 1.10.3. We identified differentially expressed genes between each perturbation and the MSCV vector controls using an adjusted p value cutoff of 0.05. We are listing the cytokines in FIG. 19 and chemokines / chemokine receptors in FIG. 20 (FC refers to Fold- Change).

[0276] At the same time, we cultured CD3+ T cells from healthy donors with a lentivirus encoding each of the mutations listed in FIG. 21 and a lentivirus encoding a chimeric antigen receptor targeting CD 19 (CAR), Kymriah®. After resting the cells in 50U / ml IL2, we cultured the cells with vesicles expressing the cognate antigen (CD 19) for 4 hours (A4) or 24 hours (A24) or with antigen negative control vesicles for 4 hours (N4) or 24 hours (N24). The samples were processed and mRNA were quantified. Differentially expressed genes were identified by DE-Seq2.0. Cytokines are listed in FIG. 21 and chemokines / chemokine receptors are shown in FIG. 22 (FC refers to Fold-Change).

[0277] Further, 1 million A375-CD19 cells were injected subcutaneously in NSG mice. CD3+ T cells from healthy human controls were transduced with a lentivirus encoding a chimeric antigen receptor targeting CD19, Kymriah®, and BTK T474M E513G or chimeric antigen receptor and a vector control. CD3+ T cells were rested in IL2 until 9 days post stimulation. After 7 additional days, after 16 days of tumor growth, IM T cells were transferred by retro-orbital injection. These cells were transferred into Nod / Scid / gamma- / --71-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 mice that were implanted with A375 cells expressing CD19. Additional controls included T cells not transduced with a CAR and phosphate buffered saline alone. The tumor volumes were measured 2-3 times a week. Mouse survivals were measured based on mouse survival and / or growth of the tumor to a pre-specified size (15 mm in any dimension). The tumor sizes were compared using 2-way ANOVA. The survival curves were compared using the log-rank test (FIG. 23). BTK T474M E513G significantly increased survival and improved tumor control.

[0278] 1 million U375 cells were injected intravenously into NSG mice. CD3+ T cells from healthy human controls were transduced with a lentivirus encoding a chimeric antigen receptor targeting CD33, scFv clone My96, and BTK T474M E513G or chimeric antigen receptor and a vector control. These cells were transferred into Nod / Scid / gamma- / - mice that were implanted with U937 cells encoding a luciferase. T cells that were untransduced served as an additional control. One to two times a week, tumor volumes were measured by luminescence as previously described (injection with 200 pl of 15 mg / ml luciferin intraperitoneally followed by imaging on Spectral instruments imaging LAGO). The tumor sizes were compared using 2-way ANOVA. The survival curves were compared using the log-rank test. BTK T474M E513G significantly increased survival and improved tumor control without inducing graft versus host disease (FIG. 24).

[0279] Materials and Methods

[0280] Genes'. Applicant selected B Cell Lymphoma (BCL) gene variants that occurred more often than expected by chance.

[0281] Codon Optimization', codon optimization was performed on selected gene variants. See e.g. Fu et al., https: / / www.nature.com / articles / s41598-020-74Q91-z (2020) for information on codon optimization, which is incorporated herein in its entirety. Codon optimization plays a role in determining protein expression.

[0282] Tumor models'. Applicant generated a syngeneic tumor bearing mice. C57BL / 6 mice obtained from Jackson Labs were inoculated subcutaneously with 0.5M B16-F10 melanoma cells that were transduced with a 51 lb vector expressing both eGFP and ovalbumin proteins.-72-4919-8127-7289.1Atty. Dkt. No.: 121384-0284[0283| In vivo retroviral screen'. Applicant cloned each of the cDNAs which encompass wild-type cDNAs as well as mutant isoforms into a barcoded murine retroviral vector. Applicant generated pools of these viruses and transduced murine T cells expressing a T cell receptor that recognizes an ovalbumin antigen, OT-I. These cells were transferred to tumor bearing mice on day 7 when the tumors were on average 100 mmA3 in size. After 7 days, the tumors were harvested, the transferred cells were isolated using cell surface markers. They were processed into genomic DNA. The barcodes were PCR amplified and sequenced by next-generation sequencing. The samples were then processed by MAGECK 2.0 to identify statistically significant genes and mutations. Positive log fold change, indicated by LFC, on tables labeled Tables 1 and 5 indicate enrichment in the solid tumor microenvironment.

[0284] Cells from tumor draining lymph nodes in the tumor bearing mice were assessed in a similar way to identify statistically significant genes and mutations.

[0285] In Vitro Validation'. For assessing the impact of the statistically significant mutations on signaling, Applicant cloned these cDNAs into a barcoded lentivirus and transduced Jurkat cells that express fluorescent reporter genes that have promoters and measure the activity of NF AT, NF-kB, and API signaling pathways. These Jurkat cells are also expressing a chimeric antigen receptor that recognizes CD 19. These cells are co-cultured with target cells (such as K562 cells) that express CD 19 (antigen-positive) or not (antigen-negative).

[0286] In Vivo Validation'. To assess effects on persistence and expansion, Applicant measured the numbers of the cells expressing the mutations or controls. To do this Applicant transduced OT-I cells with a retrovirus encoding the mutation of interest or an empty retroviral control. Applicant mixed these cells and transferred them into tumor bearing mice 9 days after tumor cell implantation. 7 days after transfer, the tumors were harvested, dissociated, and T cells were retrieved. Flow cytometry determine the relative ratios of the cells expressing the empty vector or the mutation. This ratio, normalized for differential inputs, reflects the relative enrichment or depletion compared to controls. Statistics were determined by the 2-way ANOVA test.

[0287] Tumor Control: To assess the ability of the potency enhancements to improve tumor control, Applicant transferred the cells expressing a potency enhancement or vector controls-73-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 into tumor bearing mice 9 days after tumor inoculation. Applicant measured tumor growth utilizing digital calipers every 2-3 days and calculated the volume using the formula: length x width x [(length x width)0.5] x K / 6. Applicant assessed the effects of potency enhancements on tumor control using 2-way ANOVA. Applicant also did endpoint analysis utilizing tumor length or width equal to or greater than 15 mm or greater than 50% necrosis of the tumor as clinical endpoints. Survival was measured utilizing Kaplan Meier analysis.

[0288] Peripheral Blood Expansion'. To assess the ability of potency enhancements to engraft and expand in response to antigen, Applicant performed tail vein blood collection every 3-4 days. Percentages of transferred cells were determined using flow cytometry and the congenic marker CD45.1 on transferred cells. Applicant assessed the expansion of potency enhancements in the blood using 2-way ANOVA.

[0289] Transferred Cell Persistence '. To assess adoptive cell therapy persistence and / or durability, Applicant rechallenged the mice who have completely cleared the tumor. 60 days after the initial primary tumor challenge, these mice were inoculated with 0.5M B16-F10-Ova cells that bear the tumor antigen. Tumor sizes were measured utilizing digital calipers every 2-3 days and calculated the volume using the formula: length x width x [(length x width)0.5] x 7t / 6. Applicant assessed the effects of potency enhancements on tumor control using 2-way ANOVA. Applicant also did endpoint analysis utilizing tumor length or width equal to or greater than 15mm or greater than 50% necrosis of the tumor as clinical endpoints. Survival was measured utilizing Kaplan Meier analysis.

[0290] Antigen Spread'. To assess the ability of these adoptive cell therapies to induce antigen spread, Applicant rechallenged the mice on the opposite flanks with antigen negative tumors, B16-F10 acquired from ATCC and never transduced with a vector expressing ovalbumin. 60 days after the initial primary tumor challenge, these mice were inoculated with 0.1 million B16-F10 cells that do not bear the tumor antigen. Tumor sizes were measured utilizing digital calipers every 2-3 days and calculated the volume using the formula: length x width x [(length x width)0.5] x K / 6. Applicant assessed the effects of potency enhancements on tumor control using 2-way ANOVA. Applicant also did endpoint analysis utilizing tumor length or width equal to or greater than 15 mm or greater than 50% necrosis as clinical endpoints. Survival was measured utilizing Kaplan Meier analysis. Since the transferred cells-74-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 only express OT-I, they are incapable of mediating tumor clearance directly, and antigen spread is inferred.

[0291] Tables 1 -8 shows a summary of the tested gene mutations.

[0292] Variants of interest are those which have a LFC >0 compared to the control. Wildtype proteins of interest are those which have a LFC >0 compared to the control.

[0293] Variant nomenclature is expanded upon in https: / / atlasgeneticsoncology.org / teaching / 30067 / nomenclature-for-the-description-of- mutations-and-other-sequence-variations and https: / / atlasgeneticsoncology.org / teaching / 30067 / nomenclature-for-the-description-of- mutations-and-other-sequence-variations the entire contents of which are incorporated by reference.

[0294] In the tables, the rows showing BCL10 fusion MYC-IGH and IGH-F0XP1 reflect BCL10 wild-type, MYC wild-type and FOXP1 wild-type log-fold change only, rather than fusions with IGH.

[0295] Table 1. Summary of tested gene mutations — BCL Gene variants that increase persistence in the solid tumor microenvironment LFC is log-2 fold change. Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Mutants in underlined text have a Ifc >1 and statistical significance of p<0.05 (see Table 2 for statistics).-75-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-76-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-n-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-78-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Table 2. Statistics of tested gene mutations — BCL Gene variants that increase persistence in the solid tumor microenvironment. Statistics of data presented in Table 1. Variants highlighted in underlined text in Table 1 are also highlighted in underlined text in Table 2.4919-8127-7289.1Atty. Dkt. No.: 121384-0284-80-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-81-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-82-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Table 3. BCL Genes whose variants increase persistence in the solid tumor microenvironment. Underlined text indicates statistical significance for a gene and all variants tested. Presented here are statistics for the negative scores of the mutants.-83-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-84-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Table 4. BCL Genes whose variants increase persistence in the solid tumor microenvironment. Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates statistical significance for a gene and all variants tested. Presented here are statistics for the positive scores of the mutants.-85-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-86-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Table 5. Summary of tested gene mutations — BCL Gene Variants that increase persistence in the tumor draining lymph nodes. The gene variant lists mutation. Positive Ifc (log-2 fold-87-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 change) indicates higher expression in mutant compared to the controls. Mutants in underlined text have a Ifc >1 and statistical significance of p<0.05 (see corresponding statistics in Table 6).4919-8127-7289.1Atty. Dkt. No.: 121384-0284-89-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-90-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-91-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Table 6. Statistics of tested gene mutations — BCL Gene Variants that increase persistence in the tumor draining lymph nodes. The gene variant lists mutation. Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates a mutant with statistical significance.-92-4919-8127-7289.1Aty. Dkt. No.: 121384-02844919-8127-7289.1Atty. Dkt. No.: 121384-0284-94-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-95-4919-8127-7289.1Atty. Dkt. No.: 121384-0284-96-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Table 7. BCL Genes whose variants increase persistence in the tumor draining lymph nodes. Id refers to the gene. Num refers to the number of mutations. Presented in Table 7 are negative values (negative score, p-value, fdr, rank, goodsgrna, and Ifc). Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates statistical significance. Presented here are statistics for the negative scores of the mutants.-97-4919-8127-7289.1Aty. Dkt. No.: 121384-02844919-8127-7289.1Atty. Dkt. No.: 121384-0284-99-4919-8127-7289.1Atty. Dkt. No.: 121384-0284Table 8. BCL Genes whose variants increase persistence in the tumor draining lymph nodes. Id refers to the gene. Num refers to the number of mutations. Presented in Table 7 are positive values (negative score, p-value, fdr, rank, goodsgma, and Ifc). Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates statistical significance. Presented here are statistics for the positive scores of the mutants.-100-4919-8127-7289.1Aty. Dkt. No.: 121384-02844919-8127-7289.1Atty. Dkt. No.: 121384-0284List of Sequences>SEQ ID NO: 1>BCL10 R58Q ; Length: 699 nucleotidesATGGAGCCCACCGCACCGTCCCTCACCGAGGAGGACCTCACTGAAGTGAAGAAGGACGCCTTAGAAAATTTACGTGTATACCTGTGTGAGAAAATCATAGCTGAGAGACATTTTGATCATCTACGTGCAAAAAAAATACTCAGTAGAGAAGACACTGAAGAAATTTCTTGTCAAACATCAAGTAGAAAAAGGGCTGGAAAATTGTTAGACTACTTACAGGAAAACCCAAAAGGTCTGGACACCCTTGTTGAATCTATTCGGCGAGAAAAAACACAGAACTTCCTGATACAGAAGATTACAGATGAAGTGCTGAAACTTAGAAATATAAAACTAGAACATCTGAAAGGACTAAAATGTAGCAGTTGTGAACCTTTTCCAGATGGAGCCACGAACAACCTCTCCAGATCAAATTCAGATGAGAGTAATTTCTCTGAAAAACTGAGGGCATCCACTGTCATGTACCATCCAGAAGGAGAATCCAGCACGACGCCCTTTTTTTCTACTAATTCTTCTCTGAATTTGCCTGTTCTAGAAGTAGGCAGAACTGAAAATACCATCTTCTCTTCAACTACACTTCCCAGACCTGGGGACCCAGGGGCTCCTCCTTTGCCACCAGATCTACAGTTAGAAGAAGAAGGAACTTGTGCAAACTCTAGTGAGATGTTTCTTCCCTTAAGATCACGTACTGTTTCACGACAA>SEQ ID NO: 2>BCL10 E140X ; Length: 417 nucleotidesATGGAGCCCACCGCACCGTCCCTCACCGAGGAGGACCTCACTGAAGTGAAGAAGGACGCCTTAGAAAATTTACGTGTATACCTGTGTGAGAAAATCATAGCTGAGAGACATTTTGATCATCTACGTGCAAAAAAAATACTCAGTAGAGAAGACACTGAAGAAATTTCTTGTCGAACATCAAGTAGAAAAAGGGCTGGAAAATTGTTAGACTACTTACAGGAAAACCCAAAAGGTCTGGACACCCTTGTTGAATCTATTCGGCGAGAAAAAACACAGAACTTCCTGATACAGAAGATTACAGATGAAGTGCTGAAACTTAGAAATATAAAACTAGAACATCTGAAAGGACTAAAATGTAGCAGTTGTGAACCTTTTCCAGATGGAGCCACGAACAACCTCTCCAGATCAAATTCAGAT>SEQ ID NO: 3>BCL10 L209X ; Length: 624 nucleotidesATGGAGCCCACCGCACCGTCCCTCACCGAGGAGGACCTCACTGAAGTGAAGAAGGACGCCTTAGAAAATTTACGTGTATACCTGTGTGAGAAAATCATAGCTGAGAGACATTTTGATCATCTACGTGCAAAAAAAATACTCAGTAGAGAAGACACTGAAGAAATTTCTTGTCGAACATCAAGTAGAAAAAGGGCTGGAAAATTGTTAGACTACTTACAGGAAAACCCAAAAGGTCTGGACACCCTTGTTGAATCTATTCGGCGAGAAAAAACACAGAACTTCCTGATACAGAAGATTACAGATGAAGTGCTGAAACTTAGAAATATAAAACTAGAACATCTGAAAGGACTAAAATGTAGCAGTTGTGAACCTTTTCCAGATGGAGC-102-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CACGAACAACCTCTCCAGATCAAATTCAGATGAGAGTAATTTCTCTGAAAAACTGAGGGCATCCACTGTCATGTACCATCCAGAAGGAGAATCCAGCACGACGCCCTTTTTTTCTACTAATTCTTCTCTGAATTTGCCTGTTCTAGAAGTAGGCAGAACTGAAAATACCATCTTCTCTTCAACTACACTTCCCAGACCTGGGGACCCAGGGGCTCCTCCTTTG CCACCAGATCTACAG>SEQ ID NO: 4>BCL10 wild-type ; Length: 699 nucleotidesATGGAGCCCACCGCACCGTCCCTCACCGAGGAGGACCTCACTGAAGTGAAGAAGGACGCCTTAGAAAATTTACGTGTATACCTGTGTGAGAAAATCATAGCTGAGAGACATTTTGATCATCTACGTGCAAAAAAAATACTCAGTAGAGAAGACACTGAAGAAATTTCTTGTCGAACATCAAGTAGAAAAAGGGCTGGAAAATTGTTAGACTACTTACAGGAAAACCCAAAAGGTCTGGACACCCTTGTTGAATCTATTCGGCGAGAAAAAACACAGAACTTCCTGATACAGAAGATTACAGATGAAGTGCTGAAACTTAGAAATATAAAACTAGAACATCTGAAAGGACTAAAATGTAGCAGTTGTGAACCTTTTCCAGATGGAGCCACGAACAACCTCTCCAGATCAAATTCAGATGAGAGTAATTTCTCTGAAAAACTGAGGGCATCCACTGTCATGTACCATCCAGAAGGAGAATCCAGCACGACGCCCTTTTTTTCTACTAATTCTTCTCTGAATTTGCCTGTTCTAGAAGTAGGCAGAACTGAAAATACCATCTTCTCTTCAACTACACTTCCCAGACCTGGGGACCCAGGGGCTCCTCCTTTGCCACCAGATCTACAGTTAGAAGAAGAAGGAACTTGTGCAAACTCTAGTGAGATGTTTCTTCCCTTAAGATCACGTACTGTTTCACGACAA>SEQ ID NO: 5>CTSS Y132D ; Length: 993 nucleotidesATGAAACGGCTGGTTTGTGTGCTCTTGGTGTGCTCCTCTGCAGTGGCACAGTTGCATAAAGATCCTACCCTGGATCACCACTGGCATCTCTGGAAGAAAACCTATGGCAAACAATACAAGGAAAAGAATGAAGAAGCAGTACGACGTCTCATCTGGGAAAAGAATCTAAAGTTTGTGATGCTTCACAACCTGGAGCATTCAATGGGAATGCACTCATACGATCTGGGCATGAACCACCTGGGAGACATGACCAGTGAAGAAGTGATGTCTTTGATGAGTTCCCTGAGAGTTCCCAGCCAGTGGCAGAGAAATATCACATATAAGTCAAACCCTAATCGGATATTGCCTGATTCTGTGGACTGGAGAGAGAAAGGGTGTGTTACTGAAGTGAAAGATCAAGGTTCTTGTGGTGCTTGCTGGGCTTTCAGTGCTGTGGGGGCCCTGGAAGCACAGCTGAAGCTGAAAACAGGAAAGCTGGTGTCTCTCAGTGCCCAGAACCTGGTGGATTGCTCAACTGAAAAATATGGAAACAAAGGCTGCAATGGTGGCTTCATGACAACGGCTTTCCAGTACATCATTGATAACAAGGGCATCGACTCAGACGCTTCCTATCCCTACAAAGCCATGGATCAGAAATGTCAATATGACTCAAAATATCGTGCTGCCACATGTTCAAAGTACACTGAACTTCCTTATGGCAGAGAAGATGTCCTGAAAGAAGCTGTGGCCAATAAAGGCCCAGTGTCTGTTGGTGTAGATGCGCGTCATCCTTCTTTCTTCCTCTACAGAAGTGGTGTCTACTATGAACCATCCTGTACTCAGAATGTGAATCATGGTGTACTTGTGGTTGGCTATGGTGATCTTAATGGGAAAGAATACTGGCTTGT-103-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GAAAAACAGCTGGGGCCACAACTTTGGTGAAGAAGGATATATTCGGATGGCAAGAAATAAAGGAAATCATTGTGGGATTGCTAGCTTTCCCTCTTACCCAGAAATC>SEQ ID NO: 6>API2-MALT1 Fusion ; Length: 2838 nucleotidesATGAATATTGTGGAGAACTCCATTTTTCTTTCCAACCTGATGAAGAGCGCTAATACCTTTGAGCTCAAGTATGACCTGAGTTGCGAGCTGTATAGAATGTCAACATACTCCACATTTCCCGCTGGCGTCCCAGTCAGCGAGCGGTCCTTGGCAAGAGCCGGCTTCTACTACACCGGCGTAAATGATAAAGTCAAGTGCTTTTGTTGCGGTCTGATGCTTGACAACTGGAAGCGAGGGGACTCACCAACCGAAAAGCACAAGAAGTTGTACCCCTCCTGTCGGTTCGTGCAGAGTTTGAATAGTGTGAACAACCTCGAGGCCACTAGCCAGCCTACCTTCCCATCAAGCGTCACTAACTCAACACATAGCCTGCTGCCCGGGACGGAAAATAGCGGATACTTCAGAGGCTCCTATTCAAATTCCCCAAGCAATCCCGTCAATAGTCGGGCTAATCAGGATTTCTCCGCACTCATGAGATCATCCTACCATTGTGCCATGAATAACGAGAACGCTCGTCTGCTGACCTTCCAGACATGGCCACTGACATTTCTGAGTCCTACAGATCTCGCCAAGGCAGGGTTCTACTATATTGGTCCTGGTGATCGGGTTGCCTGTTTCGCCTGCGGCGGCAAGCTGAGCAACTGGGAGCCAAAGGACAATGCAATGAGCGAGCACCTGCGCCATTTCCCCAAATGCCCATTTATCGAAAACCAACTGCAGGATACCAGCCGCTACACAGTGTCAAATCTGAGCATGCAGACACACGCGGCCAGGTTTAAAACCTTCTTTAATTGGCCATCTAGTGTGCTGGTGAACCCTGAGCAACTGGCCAGCGCCGGATTCTATTACGTAGGTAACTCCGACGACGTGAAGTGCTTTTGTTGCGACGGGGGGCTGCGGTGCTGGGAGTCTGGGGACGATCCTTGGGTACAGCATGCAAAGTGGTTCCCGAGGTGTGAGTACCTTATTAGAATCAAAGGACAGGAATTTATAAGGCAGGTCCAGGCCAGCTATCCCCATCTCCTTGAGCAGCTGCTGTCCACAAGCGACTCTCCCGGGGATGAAAATGCCGAGAGCTCAATAATCCATTTCGAGCCCGGGGAGGATCATTCTGAGGACGCCATTATGATGAACACTCCCGTTATTAATGCTGCCGTCGAGATGGGTTTTAGTCGTAGCTTAGTAAAGCAGACCGTGCAGAGAAAGATCCTTGCCACGGGAGAAAACTACCGGCTGGTGAACGACCTCGTGCTTGACCTGCTGAATGCGGAGGATGAAATCAGAGAGGAAGAACGAGAGCGCGCCACCGAAGAAAAAGAGAGCAACGAACTGAACAACTTAGGCCATCCAGATAACAAGGAACAGACTACAGACCAGCCCCTGGCTAAGGACAAAGTCGCCCTTCTCATCGGGAATATGAATTACCGAGAGCACCCAAAACTCAAAGCGCCCCTCGTCGACGTCTATGAACTGACGAATCTTCTGAGACAGTTGGATTTCAAGGTGGTTTCATTACTGGACTTAACAGAGTATGAAATGCGCAACGCCGTCGATGAGTTTCTCTTGCTTCTGGATAAAGGAGTTTATGGATTATTGTACTATGCCGGACATGGCTACGAGAACTTCGGTAACAGCTTCATGGTCCCAGTAGACGCCCCCAATCCTTATCGCAGCGAAAACTGCTTGTGCGTTCAGAATATCCTCAAGCTCATGCAGGAAAAAGAAACTGGGCTTAATGTGTTCTTGTTGGATATGTGTCGGAAACGCAATGACTACGACGACACAATACCAATCTTGGATGCGCTCAAGGTTACAGCGAATATCGTCTTCGGCTACGCAACCTGTCAAGGAGCAGAGGCGTTTGAAATCCAGCACTCAGGACTGGCTAACGGGATTTTTATGAAATTCCTGAAGGATAGGCTTCTCGAGGATAAGAAAATTACCGTGCTGCTCGACGAAGTCGCCGAAGACATGGGAAAGTGCCACTTAACTAAAGGCAAGCAGGCGTTAGAGATTCGGAGTTCCCTCAGTGAGAAACGGGCCCTCACCGATCCAATACAGGGAACTGAATACAGCGCGGAGAGCCTTGTGAGAAATCTGCAG-104-4919-8127-7289.1Atty. Dkt. No.: 121384-0284TGGGCGAAAGCACATGAGCTCCCTGAGAGCATGTGTTTGAAGTTTGATTGTGGAGTCCAGATTCAACTCGGATTTGCAGCCGAGTTTTCTAACGTCATGATAATATACACATCCATCGTCTATAAGCCACCCGAGATCATCATGTGTGACGCCTATGTTACGGACTTTCCATTGGATCTGGATATCGATCCCAAGGACGCGAATAAAGGCACACCCGAAGAGACAGGGTCCTATCTGGTGTCTAAAGACTTGCCTAAGCATTGCCTGTACACACGCCTTAGCAGTCTGCAGAAGCTTAAGGAGCATCTTGTCTTCACTGTTTGCCTCAGCTACCAGTATTCCGGGTTGGAAGATACTGTTGAGGACAAACAGGAGGTGAACGTCGGAAAACCCCTCATCGCAAAGTTAGACATGCACCGAGGACTCGGGAGAAAGACATGCTTCCAAACTTGTCTGATGTCCAACGGACCCTACCAAAGCAGTGCCGCCACTTCTGGCGGTGCGGGTCATTATCACTCATTGCAGGATCCTTTCCATGGTGTGTATCACAGTCACCCCGGCAACCCATCCAACGTAACACCTGCCGACTCCTGCCACTGTAGCCGCACTCCTGATGCATTCATTTCCAGCTTTGCGCATCACGCCAGTTGTCACTTCTCTCGATCCAACGTTCCCGTCGAAACAACGGACGAAATCCCTTTCTCTTTTTCCGACAGACTGCGGATATCAGAGAAGSEQ ID NO: 7HNRNPD G48R ; Length: 1065 nucleotidesATGTCGGAGGAGCAGTTCGGCGGGGACGGGGCGGCGGCAGCGGCAACGGCGGC GGTAGGCGGCTCGGCGGGCGAGCAGGAGGGAGCCATGGTGGCGGCGACACAGG GGGCAGCGGCGGCGGCGGGAAGCGGAGCCGGGACCAGGGGCGGAACCGCGTCT GGAGGCACCGAAGGGGGCAGCGCCGAGTCGGAGGGGGCGAAGATTGACGCCAG TAAGAACGAGGAGGATGAAGGCCATTCAAACTCCTCCCCACGACACTCTGAAGC AGCGACGGCACAGCGGGAAGAATGGAAAATGTTTATAGGAGGCCTTAGCTGGGA CACTACAAAGAAAGATCTGAAGGACTACTTTTCCAAATTTGGTGAAGTTGTAGAC TGCACTCTGAAGTTAGATCCTATCACAGGGCGATCAAGGGGTTTTGGCTTTGTGCT ATTTAAAGAATCGGAGAGTGTAGATAAGGTCATGGATCAAAAAGAACATAAATTG AATGGGAAGGTGATTGATCCTAAAAGGGCCAAAGCCATGAAAACAAAAGAGCCG GTTAAAAAAATTTTTGTTGGTGGCCTTTCTCCAGATACACCTGAAGAGAAAATAAG GGAGTACTTTGGTGGTTTTGGTGAGGTGGAATCCATAGAGCTCCCCATGGACAAC AAGACCAATAAGAGGCGTGGGTTCTGCTTTATTACCTTTAAGGAAGAAGAACCAG TGAAGAAGATAATGGAAAAGAAATACCACAATGTTGGTCTTAGTAAATGTGAAATA AAAGTAGCCATGTCGAAGGAACAATATCAGCAACAGCAACAGTGGGGATCTAGAG GAGGATTTGCAGGAAGAGCTCGTGGAAGAGGTGGTGGCCCCAGTCAAAACTGGA ACCAGGGATATAGTAACTATTGGAATCAAGGCTATGGCAACTATGGATATAACAGC CAAGGTTACGGTGGTTATGGAGGATATGACTACACTGGTTACAACAACTACTATGG ATATGGTGATTATAGCAACCAGCAGAGTGGTTATGGGAAGGTATCCAGGCGAGGTG GTCATCAAAATAGCTACAAACCATAC> SEQ ID NO: 8> FOXO1 T24I ; Length: 1965 nucleotides-105-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ATGGCCGAGGCGCCTCAGGTGGTGGAGATCGACCCGGACTTCGAGCCGCTGCCCCGGCCGCGCTCGTGCATCTGGCCGCTGCCCAGGCCGGAGTTTAGCCAGTCCAACTCGGCCACCTCCAGCCCGGCGCCGTCGGGCAGCGCGGCTGCCAACCCCGACGCCGCGGCGGGCCTGCCCTCGGCCTCGGCTGCCGCTGTCAGCGCCGACTTCATGAGCAACCTGAGCTTGCTGGAGGAGAGCGAGGACTTCCCGCAGGCGCCCGGCTCCGTGGCGGCGGCGGTGGCGGCGGCGGCCGCCGCGGCCGCCACCGGGGGGCTGTGCGGGGACTTCCAGGGCCCGGAGGCGGGCTGCCTGCACCCAGCGCCACCGCAGCCCCCGCCGCCCGGGCCGCTGTCGCAGCACCCGCCGGTGCCCCCCGCCGCCGCTGGGCCGCTCGCGGGGCAGCCGCGCAAGAGCAGCTCGTCCCGCCGCAACGCGTGGGGCAACCTGTCCTACGCCGACCTCATCACCAAGGCCATCGAGAGCTCGGCGGAGAAGCGGCTCACGCTGTCGCAGATCTACGAGTGGATGGTCAAGAGCGTGCCCTACTTCAAGGATAAGGGTGACAGCAACAGCTCGGCGGGCTGGAAGAATTCAATTCGTCATAATCTGTCCCTACACAGCAAGTTCATTCGTGTGCAGAATGAAGGAACTGGAAAAAGTTCTTGGTGGATGCTCAATCCAGAGGGTGGCAAGAGCGGGAAATCTCCTAGGAGAAGAGCTGCATCCATGGACAACAACAGTAAATTTGCTAAGAGCCGAAGCCGAGCTGCCAAGAAGAAAGCATCTCTCCAGTCTGGCCAGGAGGGTGCTGGGGACAGCCCTGGATCACAGTTTTCCAAATGGCCTGCAAGCCCTGGCTCTCACAGCAATGATGACTTTGATAACTGGAGTACATTTCGCCCTCGAACTAGCTCAAATGCTAGTACTATTAGTGGGAGACTCTCACCCATTATGACCGAACAGGATGATCTTGGAGAAGGGGATGTGCATTCTATGGTGTACCCGCCATCTGCCGCAAAGATGGCCTCTACTTTACCCAGTCTGTCTGAGATAAGCAATCCCGAAAACATGGAAAATCTTTTGGATAATCTCAACCTTCTCTCATCACCAACATCATTAACTGTTTCGACCCAGTCCTCACCTGGCACCATGATGCAGCAGACGCCGTGCTACTCGTTTGCGCCACCAAACACCAGTTTGAATTCACCCAGCCCAAACTACCAAAAATATACATATGGCCAATCCAGCATGAGCCCTTTGCCCCAGATGCCTATACAAACACTTCAGGACAATAAGTCGAGTTATGGAGGTATGAGTCAGTATAACTGTGCGCCTGGACTCTTGAAGGAGTTGCTGACTTCTGACTCTCCTCCCCATAATGACATTATGACACCAGTTGATCCTGGGGTAGCCCAGCCCAACAGCCGGGTTCTGGGCCAGAACGTCATGATGGGCCCTAATTCGGTCATGTCAACCTATGGCAGCCAGGCATCTCATAACAAAATGATGAATCCCAGCTCCCATACCCACCCTGGACATGCTCAGCAGACATCTGCAGTTAACGGGCGTCCCCTGCCCCACACGGTAAGCACCATGCCCCACACCTCGGGTATGAACCGCCTGACCCAAGTGAAGACACCTGTACAAGTGCCTCTGCCCCACCCCATGCAGATGAGTGCCCTGGGGGGCTACTCCTCCGTGAGCAGCTGCAATGGCTATGGCAGAATGGGCCTTCTCCACCAGGAGAAGCTCCCAAGTGACTTGGATGGCATGTTCATTGAGCGCTTAGACTGTGACATGGAATCCATCATTCGGAATGACCTCATGGATGGAGATACATTGGATTTTAACTTTGACAATGTGTTGCCCAACCAAAGCTTCCCACACAGTGTCAAGACAACGACACATAGCTGGGTGTCAGGC> SEQ ID NO: 9> MEF2C N389S ; Length: 1419 nucleotidesATGGGGAGAAAAAAGATTCAGATTACGAGGATTATGGATGAACGTAACAGACAGGTGACATTTACAAAGAGGAAATTTGGGTTGATGAAGAAGGCTTATGAGCTGAGCGTGCTGTGTGACTGTGAGATTGCGCTGATCATCTTCAACAGCACCAACAAGCTGTTCCAGTATGCCAGCACCGACATGGACAAAGTGCTTCTCAAGTACACGGAGTACAACGA-106-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GCCGCATGAGAGCCGGACAAACTCAGACATCGTGGAGACGTTGAGAAAGAAGGGCCTTAATGGCTGTGACAGCCCAGACCCCGATGCGGACGATTCCGTAGGTCACAGCCCTGAGTCTGAGGACAAGTACAGGAAAATTAACGAAGATATTGATCTAATGATCAGCAGGCAAAGATTGTGTGCTGTTCCACCTCCCAACTTCGAGATGCCAGTCTCCATCCCAGTGTCCAGCCACAACAGTTTGGTGTACAGCAACCCTGTCAGCTCACTGGGAAACCCCAACCTATTGCCACTGGCTCACCCTTCTCTGCAGAGGAATAGTATGTCTCCTGGTGTAACACATCGACCTCCAAGTGCAGGTAACACAGGTGGTCTGATGGGTGGAGACCTCACGTCTGGTGCAGGCACCAGTGCAGGGAACGGGTATGGCAATCCCCGAAACTCACCAGGTCTGCTGGTCTCACCTGGTAACTTGAACAAGAATATGCAAGCAAAATCTCCTCCCCCAATGAATTTAGGAATGAATAACCGTAAACCAGATCTCCGAGTTCTTATTCCACCAGGCAGCAAGAATACGATGCCATCAGTGTCTGAGGATGTCGACCTGCTTTTGAATCAAAGGATAAATAACTCCCAGTCGGCTCAGTCATTGGCTACCCCAGTGGTTTCCGTAGCAACTCCTACTTTACCAGGACAAGGAATGGGAGGATATCCATCAGCCATTTCAACAACATATGGTACCGAGTACTCTCTGAGTAGTGCAGACCTGTCATCTCTGTCTGGGTTTAACACCGCCAGCGCTCTTCACCTTGGTTCAGTAACTGGCTGGCAACAGCAACACCTACATAACATGCCACCATCTGCCCTCAGTCAGTTGGGAGCTTGCACTAGCACTCATTTATCTCAGAGTTCAAATCTCTCCCTGCCTTCTACTCAAAGCCTCAGCATCAAGTCAGAACCTGTTTCTCCTCCTAGAGACCGTACCACCACCCCTTCGAGATACCCACAACACACGCGCCACGAGGCGGGGAGATCTCCTGTTGACAGCTTGAGCAGCTGTAGCAGTTCGTACGACGGGAGCGACCGAGAGGATCACCGGAACGAATTCCACTCCCCCATTGGACTCACCAGACCTTCGCCGGACGAAAGGGAAAGTCCCTCAGTCAAGCGCATGCGACTTTCTGAAGGATGGGCAACA> SEQ ID NO: 10> HIST1H1E A158T ; Length: 657 nucleotidesATGTCCGAGACTGCGCCTGCCGCGCCCGCTGCTCCGGCCCCTGCCGAGAAGACTCCCGTGAAGAAGAAGGCCCGCAAGTCTGCAGGTGCGGCCAAGCGCAAAGCGTCTGGGCCCCCGGTGTCCGAGCTCATTACTAAAGCTGTTGCCGCCTCCAAGGAGCGCAGCGGCGTATCTTTGGCCGCTCTCAAGAAAGCGCTGGCAGCCGCTGGCTATGACGTGGAGAAGAACAACAGCCGCATCAAGCTGGGTCTCAAGAGCCTGGTGAGCAAGGGCACCCTGGTGCAGACCAAGGGCACCGGCGCGTCGGGTTCCTTCAAACTCAACAAGAAGGCGGCCTCTGGGGAAGCCAAGCCTAAGGCTAAAAAGGCAGGCGCGGCCAAGGCCAAGAAGCCAGCAGGAGCGGCGAAGAAGCCCAAGAAGGCGACGGGGGCGGCCACCCCCAAGAAGAGCGCCAAGAAGACCCCAAAGAAGACGAAGAAGCCGGCTGCAGCTGCTGGAGCCAAAAAAGCGAAAAGCCCGAAAAAGGCGAAAGCAGCCAAGCCAAAAAAGGCGCCCAAGAGCCCAGCGAAGGCCAAAGCAGTTAAACCCAAGGCGGCTAAACCAAAGACCGCCAAGCCCAAGGCAGCCAAGCCAAAGAAGGCGGCAGCCAAGAAAAAG> SEQ ID NO: 11> IRF8 Y23H ; Length: 378 nucleotides-107-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ATGTGTGACCGGAATGGTGGTCGGCGGCTTCGACAGTGGCTGATCGAGCAGATTGACAGTAGCATGCATCCAGGACTGATTTGGGAGAATGAGGAGAAGAGCATGTTCCGGATCCCTTGGAAACACGCTGGCAAGCAAGATTATAATCAGGAAGTGGATGCCTCCATTTTTAAGGCCTGGGCAGTTTTTAAAGGGAAGTTTAAAGAAGGGGACAAAGCTGAACCAGCCACTTGGAAGACGAGGTTACGCTGTGCTTTGAATAAGAGCCCAGATTTTGAGGAAGTGACGGACCGGTCCCAACTGGACATTTCCGAGCCATACAAAGTTTACCGAATTGTTCCTGAGGAAGAGCAAAAATGTAACTATCCTTTATGGGCA> SEQ ID NO: 12> HRAS S145L ; Length: 567 nucleotidesATGACGGAATATAAGCTGGTGGTGGTGGGCGCCGGCGGTGTGGGCAAGAGTGCGCTGACCATCCAGCTGATCCAGAACCATTTTGTGGACGAATACGACCCCACTATAGAGGATTCCTACCGGAAGCAGGTGGTCATTGATGGGGAGACGTGCCTGTTGGACATCCTGGATACCGCCGGCCAGGAGGAGTACAGCGCCATGCGGGACCAGTACATGCGCACCGGGGAGGGCTTCCTGTGTGTGTTTGCCATCAACAACACCAAGTCTTTTGAGGACATCCACCAGTACAGGGAGCAGATCAAACGGGTGAAGGACTCGGATGACGTGCCCATGGTGCTGGTGGGGAACAAGTGTGACCTGGCTGCACGCACTGTGGAATCTCGGCAGGCTCAGGACCTCGCCCGAAGCTACGGCATCCCCTACATCGAGACCTTGGCCAAGACCCGGCAGGGAGTGGAGGATGCCTTCTACACGTTGGTGCGTGAGATCCGGCAGCACAAGCTGCGGAAGCTGAACCCTCCTGATGAGAGTGGCCCCGGCTGCATGAGCTGCAAGTGTGTGCTCTCC> SEQ ID NO: 13> MEF2B D83V ; Length: 891 nucleotidesATGGGGAGGAAAAAAATCCAGATCTCCCGCATCCTGGACCAAAGGAATCGGCAGGTGACGTTCACCAAGCGGAAGTTCGGGCTGATGAAGAAGGCCTATGAGCTGAGCGTGCTCTGTGACTGTGAGATAGCCCTCATCATCTTCAACAGCGCCAACCGCCTCTTCCAGTATGCCAGCACGGACATGGACCGTGTGCTGCTGAAGTACACAGAGTACAGCGAGCCCCACGAGAGCCGCACCAACACTGTCATCCTCGAGGTACCCCAGACGCTGAAGCGGAGGGGCATTGGCCTCGATGGGCCAGAGCTGGAGCCGGATGAAGGGCCTGAGGAGCCAGGAGAGAAGTTTCGGAGGCTGGCAGGCGAAGGGGGTGATCCGGCCTTGCCCCGACCCCGGCTGTATCCTGCAGCTCCTGCTATGCCCAGCCCAGATGTGGTATACGGGGCCTTACCGCCACCAGGCTGTGACCCCAGTGGGCTTGGGGAAGCACTGCCCGCCCAGAGCCGCCCATCTCCCTTCCGACCAGCAGCCCCCAAAGCCGGGCCCCCAGGCCTGGTGCACCCTCTCTTCTCACCAAGCCACCTCACCAGCAAGACACCACCCCCACTGTACCTGCCGACGGAAGGGCGGAGGTCAGACCTGCCTGGTGGCCTGGCTGGGCCCCGAGGGGGACTAAACACCTCCAGAAGCCTCTACAGTGGCCTGCAGAACCCCTGCTCCACTGCAACTCCCGGACCCCCACTGGGGAGCTTCCCCTTCCTCCCCGGAGGCCCCCCAGAATATGGCCTGGGAGACCCTCCACCGCCCCCTGGCTTGTTG-108-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CAGCCCCCCACCCTGGCCCCCTGGCAGCCCTCGAGGGGTGATGGGCCCCCCGCCGTGTCCTCCCAGCCCAGG> SEQ ID NO: 14> BTK T474M+E513G ; Length: 1980 nucleotidesATGGCCGCAGTGATTCTGGAGAGCATCTTTCTGAAGCGATCCCAACAGAAAAAGAAAACATCACCTCTAAACTTCAAGAAGCGCCTGTTTCTCTTGACCGTGCACAAACTCTCCTACTATGAGTATGACTTTGAACGTGGGAGAAGAGGCAGTAAGAAGGGTTCAATAGATGTTGAGAAGATCACTTGTGTTGAAACAGTGGTTCCTGAAAAAAATCCTCCTCCAGAAAGACAGATTCCGAGAAGAGGTGAAGAGTCCAGTGAAATGGAGCAAATTTCAATCATTGAAAGGTTCCCTTATCCCTTCCAGGTTGTATATGATGAAGGGCCTCTCTACGTCTTCTCCCCAACTGAAGAACTAAGGAAGCGGTGGATTCACCAGCTCAAAAACGTAATCCGGTACAACAGTGATCTGGTTCAGAAATATCACCCTTGCTTCTGGATCGATGGGCAGTATCTCTGCTGCTCTCAGACAGCCAAAAATGCTATGGGCTGCCAAATTTTGGAGAACAGGAATGGAAGCTTAAAACCTGGGAGTTCTCACCGGAAGACAAAAAAGCCTCTTCCCCCAACGCCTGAGGAGGACCAGATCTTGAAAAAGCCACTACCGCCTGAGCCAGCAGCAGCACCAGTCTCCACAAGTGAGCTGAAAAAGGTTGTGGCCCTTTATGATTACATGCCAATGAATGCAAATGATCTACAGCTGCGGAAGGGTGATGAATATTTTATCTTGGAGGAAAGCAACTTACCATGGTGGAGAGCACGAGATAAAAATGGGCAGGAAGGCTACATTCCTAGTAACTATGTCACTGAAGCAGAAGACTCCATAGAAATGTATGAGTGGTATTCCAAACACATGACTCGGAGTCAGGCTGAGCAACTGCTAAAGCAAGAGGGGAAAGAAGGAGGTTTCATTGTCAGAGACTCCAGCAAAGCTGGCAAATATACAGTGTCTGTGTTTGCTAAATCCACAGGGGACCCTCAAGGGGTGATACGTCATTATGTTGTGTGTTCCACACCTCAGAGCCAGTATTACCTGGCTGAGAAGCACCTTTTCAGCACCATCCCTGAGCTCATTAACTACCATCAGCACAACTCTGCAGGACTCATATCCAGGCTCAAATATCCAGTGTCTCAACAAAACAAGAATGCACCTTCCACTGCAGGCCTGGGATACGGATCATGGGAAATTGATCCAAAGGACCTGACCTTCTTGAAGGAGCTGGGGACTGGACAATTTGGGGTAGTGAAGTATGGGAAATGGAGAGGCCAGTACGACGTGGCCATCAAGATGATCAAAGAAGGCTCCATGTCTGAAGATGAATTCATTGAAGAAGCCAAAGTCATGATGAATCTTTCCCATGAGAAGCTGGTGCAGTTGTATGGCGTCTGCACCAAGCAGCGCCCCATCTTCATCATCATGGAGTACATGGCCAATGGCTGCCTCCTGAACTACCTGAGGGAGATGCGCCACCGCTTCCAGACTCAGCAGCTGCTAGAGATGTGCAAGGATGTCTGTGAAGCCATGGAATACCTGGGGTCAAAGCAGTTCCTTCACCGAGACCTGGCAGCTCGAAACTGTTTGGTAAACGATCAAGGAGTTGTTAAAGTATCTGATTTCGGCCTGTCCAGGTATGTCCTGGATGATGAATACACAAGCTCAGTAGGCTCCAAATTTCCAGTCCGGTGGTCCCCACCGGAAGTCCTGATGTATAGCAAGTTCAGCAGCAAATCTGACATTTGGGCTTTTGGGGTTTTGATGTGGGAAATTTACTCCCTGGGGAAGATGCCATATGAGAGATTTACTAACAGTGAGACTGCTGAACACATTGCCCAAGGCCTACGTCTCTACAGGCCTCATCTGGCTTCAGAGAAGGTATATACCATCATGTACAGTTGCTGGCATGAGAAAGCAGATGAGCGTCCCACTTTCAAAATTCTTCTGAGCAATATTCTAGATGTCATGGATGAAGAATCCTGA-109-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> SEQ ID NO: 15> IKBKB K171T ; Length: 768 nucleotidesATGAGCTGGTCACCTTCCCTGACAACGCAGACATGTGGGGCCTGGGAAATGAAAGAGCGCCTTGGGACAGGGGGATTTGGAAATGTCATCCGATGGCACAATCAGGAAACAGGTGAGCAGATTGCCATCAAGCAGTGCCGGCAGGAGCTCAGCCCCCGGAACCGAGAGCGGTGGTGCCTGGAGATCCAGATCATGAGAAGGCTGACCCACCCCAATGTGGTGGCTGCCCGAGATGTCCCTGAGGGGATGCAGAACTTGGCGCCCAATGACCTGCCCCTGCTGGCCATGGAGTACTGCCAAGGAGGAGATCTCCGGAAGTACCTGAACCAGTTTGAGAACTGCTGTGGTCTGCGGGAAGGTGCCATCCTCACCTTGCTGAGTGACATTGCCTCTGCGCTTAGATACCTTCATGAAAACAGAATCATCCATCGGGATCTAAAGCCAGAAAACATCGTCCTGCAGCAAGGAGAACAGAGGTTAATACACAAAATTATTGACCTAGGATATGCCACGGAGCTGGATCAGGGCAGTCTTTGCACATCATTCGTGGGGACCCTGCAGTACCTGGCCCCAGAGCTACTGGAGCAGCAGAAGTACACAGTGACCGTCGACTACTGGAGCTTCGGCACCCTGGCCTTTGAGTGCATCACGGGCTTCCGGCCCTTCCTCCCCAACTGGCAGCCCGTGCAGTGCGTAAGAATGTGGCCGGGTACAGTGGCTCACTCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCAGGTGGATCAGT> SEQ ID NO: 16> BCL2 T7I ; Length: 717 nucleotidesATGGCGCACGCTGGGAGAATAGGGTACGATAACCGGGAGATAGTGATGAAGTACATCCATTATAAGCTGTCGCAGAGGGGCTACGAGTGGGATGCGGGAGATGTGGGCGCCGCGCCCCCGGGGGCCGCCCCCGCACCGGGCATCTTCTCCTCCCAGCCCGGGCACACGCCCCATCCAGCCGCATCCCGGGACCCGGTCGCCAGGACCTCGCCGCTGCAGACCCCGGCTGCCCCCGGCGCCGCCGCGGGGCCTGCGCTCAGCCCGGTGCCACCTGTGGTCCACCTGACCCTCCGCCAGGCCGGCGACGACTTCTCCCGCCGCTACCGCCGCGACTTCGCCGAGATGTCCAGCCAGCTGCACCTGACGCCCTTCACCGCGCGGGGACGCTTTGCCACGGTGGTGGAGGAGCTCTTCAGGGACGGGGTGAACTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCATGTGTGTGGAGAGCGTCAACCGGGAGATGTCGCCCCTGGTGGACAACATCGCCCTGTGGATGACTGAGTACCTGAACCGGCACCTGCACACCTGGATCCAGGATAACGGAGGCTGGGATGCCTTTGTGGAACTGTACGGCCCCAGCATGCGGCCTCTGTTTGATTTCTCCTGGCTGTCTCTGAAGACTCTGCTCAGTTTGGCCCTGGTGGGAGCTTGCATCACCCTGGGTGCCTATCTGGGCCACAAG> SEQ ID NO: 17> BCL2 G33R ; Length: 615 nucleotidesATGGCGCACGCTGGGAGAACAGGGTACGATAACCGGGAGATAGTGATGAAGTACATCCATTATAAGCTGTCGCAGAGGGGCTACGAGTGGGATGCGAGAGATGTGGGCGC-110-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CGCGCCCCCGGGGGCCGCCCCCGCACCGGGCATCTTCTCCTCCCAGCCCGGGCACACGCCCCATCCAGCCGCATCCCGGGACCCGGTCGCCAGGACCTCGCCGCTGCAGACCCCGGCTGCCCCCGGCGCCGCCGCGGGGCCTGCGCTCAGCCCGGTGCCACCTGTGGTCCACCTGACCCTCCGCCAGGCCGGCGACGACTTCTCCCGCCGCTACCGCCGCGACTTCGCCGAGATGTCCAGCCAGCTGCACCTGACGCCCTTCACCGCGCGGGGACGCTTTGCCACGGTGGTGGAGGAGCTCTTCAGGGACGGGGTGAACTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCATGTGTGTGGAGAGCGTCAACCGGGAGATGTCGCCCCTGGTGGACAACATCGCCCTGTGGATGACTGAGTACCTGAACCGGCACCTGCACACCTGGATCCAGGATAACGGAGGCTGGGTAGGTGCACTTGGTGATG TGAGTCTGGGC> SEQ ID NO: 18> CARD 11 C49Y ; Length 3462ATGCCAGGAGGAGGGCCAGAGATGGATGACTACATGGAGACGCTGAAGGATGAAGAGGACGCCTTGTGGGAGAATGTGGAGTGTAACCGGCACATGCTCAGCCGCTATATCAACCCTGCCAAGCTCACGCCCTACCTGCGTCAGTATAAGGTCATTGATGAGCAGGATGAAGATGAAGTGCTTAATGCCCCTATGCTGCCATCCAAGATCAACCGAGCAGGCCGGCTGTTGGACATTCTACATACCAAGGGGCAAAGGGGCTATGTGGTCTTCTTGGAGAGCCTAGAATTTTATTACCCAGAACTGTACAAACTGGTGACTGGGAAAGAGCCCACTCGGAGATTCTCCACCATTGTGGTGGAGGAAGGCCACGAGGGCCTCACGCACTTCCTGATGAACGAGGTCATCAAGCTGCAGCAGCAGATGAAGGCCAAGGACCTGCAACGCTGCGAGCTGCTGGCCAGGTTGCGGCAGCTGGAGGATGAGAAGAAGCAGATGACGCTGACGCGCGTGGAGCTGCTAACCTTCCAGGAGCGGTACTACAAGATGAAGGAAGAGCGGGACAGCTACAATGACGAGCTGGTCAAGGTGAAGGACGACAACTACAACTTAGCCATGCGCTACGCACAGCTCAGTGAGGAGAAGAACATGGCGGTCATGAGGAGCCGAGACCTCCAACTCGAGATCGATCAGCTAAAGCACCGGTTGAATAAGATGGAGGAGGAATGTAAGCTGGAGAGAAATCAGTCTCTAAAACTGAAGAATGACATTGAAAATCGGCCCAAGAAGGAGCAGGTTCTGGAACTGGAGCGGGAGAATGAAATGCTGAAGACCAAAAACCAGGAGCTGCAGTCCATCATCCAGGCCGGGAAGCGCAGCCTGCCAGACTCAGACAAGGCCATCCTGGACATCTTGGAACACGACCGCAAGGAGGCCCTGGAGGACAGGCAGGAGCTGGTCAACAGGATCTACAACCTGCAGGAGGAGGCCCGCCAGGCAGAGGAGCTGCGAGACAAGTACCTGGAGGAGAAGGAGGACCTGGAGCTCAAGTGCTCGACCCTGGGAAAGGACTGTGAAATGTACAAGCACCGCATGAACACGGTCATGCTGCAGCTGGAGGAGGTGGAGCGGGAGCGGGACCAGGCCTTCCACTCCCGAGATGAAGCTCAGACACAGTACTCGCAGTGCTTAATCGAAAAGGACAAGTACAGGAAGCAGATCCGCGAGCTGGAGGAGAAGAACGACGAGATGAGGATCGAGATGGTGCGGCGGGAGGCCTGCATCGTCAACCTGGAGAGCAAGCTGCGGCGCCTCTCCAAGGACAGCAACAACCTGGACCAGAGTCTGCCCAGGAACCTGCCAGTAACCATCATCTCTCAGGACTTTGGGGATGCCAGCCCCAGGACCAATGGTCAAGAAGCTGACGATTCTTCCACCTCGGAGGAGTCACCTGAAGACAGCAAGTACTTCCTGCCCTACCATCCGCCCCAGCGCAGGATGAACCTGAAGGGCATCCAGCTGCAGAGAGCCAAATCCCCCATCAGCCTGAAGCGAACATCAGATTTTCAAGCCAAGGGGCACGAGGAAGAAGGCACGGACGCCAGCCCTAGCTCCTGCGGATCTCTGCCCATCACCAACTC-I l l-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CTTCACCAAGATGCAGCCCCCCCGGAGCCGCAGCAGCATCATGTCAATCACCGCCGAGCCCCCGGGAAACGACTCCATCGTCAGACGCTACAAGGAGGACGCGCCCCATCGCAGCACAGTCGAAGAAGACAATGACAGCGGCGGGTTTGACGCCTTAGATCTG GATGATGACAGTCACGAACGCTACTCCTTCGGACCCTCCTCCATCCACTCCTCCTC CTCCTCCCACCAATCCGAGGGCCTGGATGCCTACGACCTGGAGCAGGTCAACCTC ATGTTCAGGAAGTTCTCTCTGGAAAGACCCTTCCGGCCTTCGGTCACCTCTGTGGGGCACGTGCGGGGCCCAGGGCCCTCGGTGCAGCACACGACGCTGAATGGCGACAGCCTCACCTCCCAGCTCACCCTGCTGGGGGGCAACGCGCGAGGGAGCTTCGTGCACTCGGTCAAGCCTGGCTCTCTGGCCGAGAAAGCCGGCCTCCGTGAGGGCCACCAGCTGCTGCTGCTAGAAGGCTGCATCCGAGGCGAGAGGCAGAGTGTCCCGTTGG ACACATGCACCAAAGAGGAAGCCCACTGGACCATCCAGAGGTGCAGCGGCCCCG TCACGCTGCACTACAAGGTCAACCACGAAGGGTACCGGAAGCTGGTGAAGGACA TGGAGGACGGCCTGATCACATCGGGGGACTCGTTCTACATCCGGCTGAACCTGAACATCTCCAGCCAGCTGGACGCCTGCACCATGTCCCTGAAGTGTGACGATGTTGTGCACGTCCGTGACACCATGTACCAGGACAGGCACGAGTGGCTGTGCGCGCGGGTCGACCCTTTCACAGACCATGACCTGGATATGGGCACCATACCCAGCTACAGCCGAGCCCAGCAGCTCCTCCTGGTGAAACTGCAGCGCCTGATGCACCGAGGCAGCCGGG AGGAGGTAGACGGCACCCACCACACCCTGCGGGCACTCCGGAACACCCTGCAGC CAGAAGAAGCGCTTTCAACAAGCGACCCCCGGGTCAGCCCCCGTCTCTCGCGAG CAAGCTTCCTTTTTGGCCAGCTCCTTCAGTTCGTCAGCAGGTCCGAGAACAAGTATAAGCGGATGAACAGCAACGAGCGGGTCCGCATCATCTCGGGGAGTCCGCTAGGG AGCCTGGCCCGGTCCTCGCTGGACGCCACCAAGCTCTTGACTGAGAAGCAGGAA GAGCTGGACCCTGAGAGCGAGCTGGGCAAGAACCTCAGCCTCATCCCCTACAGC CTGGTACGCGCCTTCTACTGCGAGCGCCGCCGGCCCGTGCTCTTCACACCCACCGTGCTGGCCAAGACGCTGGTGCAGAGGCTGCTCAACTCGGGAGGTGCCATGGAGT TCACCATCTGCAAGTCAGATATCGTCACAAGAGATGAGTTCCTCAGAAGGCAGAA GACGGAGACCATCATCTACTCCCGAGAGAAGAACCCCAACGCGTTCGAATGCATC GCCCCTGCCAACATTGAAGCTGTGGCCGCCAAGAACAAGCACTGCCTGCTGGAGGCTGGGATCGGCTGCACAAGAGACTTGATCAAGTCCAACATCTACCCCATCGTGC TCTTCATCCGGGTGTGTGAGAAGAACATCAAGAGGTTCAGAAAGCTGCTGCCCCG ACCTGAGACGGAGGAGGAGTTCCTGCGCGTGTGCCGGCTGAAGGAGAAGGAGCT GGAGGCCCTGCCGTGCCTGTACGCCACGGTGGAACCTGACATGTGGGGCAGCGTAGAGGAGCTGCTCCGCGTTGTCAAGGACAAGATCGGCGAGGAGCAGCGCAAGACC ATCTGGGTGGACGAGGACCAGCTG> SEQ ID NO: 19> MYD88 L265P ; Length: 927 nucleotidesATGCGACCCGACCGCGCTGAGGCTCCAGGACCGCCCGCCATGGCTGCAGGAGGTCCCGGCGCGGGGTCTGCGGCCCCGGTCTCCTCCACATCCTCCCTTCCCCTGGCTGCTCTCAACATGCGAGTGCGGCGCCGCCTGTCTCTGTTCTTGAACGTGCGGACACAGGTGGCGGCCGACTGGACCGCGCTGGCGGAGGAGATGGACTTTGAGTACTTGGAGATCCGGCAACTGGAGACACAAGCGGACCCCACTGGCAGGCTGCTGGACGCCTGGCAGGGACGCCCTGGCGCCTCTGTAGGCCGACTGCTCGAGCTGCTTACCAAGCTGG-112-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GCCGCGACGACGTGCTGCTGGAGCTGGGACCCAGCATTGAGGAGGATTGCCAAAAGTATATCTTGAAGCAGCAGCAGGAGGAGGCTGAGAAGCCTTTACAGGTGGCCGCTGTAGACAGCAGTGTCCCACGGACAGCAGAGCTGGCGGGCATCACCACACTTGATGACCCCCTGGGGCATATGCCTGAGCGTTTCGATGCCTTCATCTGCTATTGCCCCAGCGACATCCAGTTTGTGCAGGAGATGATCCGGCAACTGGAACAGACAAACTATCGACTGAAGTTGTGTGTGTCTGACCGCGATGTCCTGCCTGGCACCTGTGTCTGGTCTATTGCTAGTGAGCTCATCGAAAAGAGGTGCCGCCGGATGGTGGTGGTTGTCTCTGATGATTACCTGCAGAGCAAGGAATGTGACTTCCAGACCAAATTTGCACTCAGCCTCTCTCCAGGTGCCCATCAGAAGCGACCGATCCCCATCAAGTACAAGGCAATGAAGAAAGAGTTCCCCAGCATCCTGAGGTTCATCACTGTCTGCGACTACACCAACCCCTGCACCAAATCTTGGTTCTGGACTCGCCTTGCCAAGGCCTTGTCCCTGCCC> SEQ ID NO: 20> KLF2 A291T ; Length: 1065 nucleotidesATGGCGCTGAGTGAACCCATCCTGCCGTCCTTCTCCACTTTCGCCAGCCCGTGCCGCGAGCGCGGCCTGCAGGAGCGCTGGCCGCGCGCCGAACCCGAGTCCGGCGGCACCGACGACGACCTCAACAGCGTGCTGGACTTCATCCTGTCCATGGGGCTGGATGGCCTGGGCGCCGAGGCCGCCCCGGAGCCGCCGCCGCCGCCCCCGCCGCCTGCGTTCTATTACCCCGAACCCGGCGCGCCCCCGCCCTACAGCGCCCCCGCGGGTGGCCTGGTGTCTGAGCTGCTGCGACCCGAGCTGGATGCGCCGCTGGGGCCCGCACTGCACGGCCGCTTTCTGCTGGCGCCGCCCGGCCGCCTGGTCAAGGCCGAGCCCCCTGAAGCGGACGGCGGCGGCGGCTACGGCTGCGCCCCCGGGCTGACCCGTGGACCGCGCGGCCTCAAGCGCGAGGGCGCCCCGGGCCCGGCGGCTTCGTGCATGCGAGGTCCCGGGGGCCGCCCCCCGCCGCCGCCCGACACACCGCCGCTCAGCCCCGACGGCCCCGCGCGCCTGCCCGCGCCCGGTCCGCGCGCCTCCTTCCCGCCGCCTTTCGGTGGCCCTGGTTTCGGCGCGCCCGGGCCCGGCCTGCATTACGCGCCGCCTGCGCCCCCAGCCTTCGGTCTCTTCGACGACGCGGCCGCCGCCGCGGCAGCCCTGGGCCTGGCGCCCCCCGCCGCCCGCGGTCTCCTCACGCCGCCTGCGTCCCCGCTGGAGCTGCTGGAGGCCAAGCCAAAGCGCGGCCGCCGCTCTTGGCCCCGCAAACGCACCGCCACTCACACCTGCAGCTACGCGGGCTGCGGCAAGACCTACACCAAGAGTTCGCATCTGAAGACGCATCTGCGCACGCACACAGGTGAGAAGCCCTACCACTGCAACTGGGACGGCTGCGGCTGGAAGTTTGCGCGCTCAGACGAGCTCACGCGCCACTACCGAAAGCACACGGGCCACCGGCCATTCCAGTGCCATCTGTGCGATCGTGCCTTCTCGCGCTCCGATCACCT GGCGCTGCACATGAAACGGCACATG> SEQ ID NO: 21> MYC wild-type; Length: 1362 nucleotidesATGGATTTTTTTCGGGTAGTGGAAAACCAGCAGCCTCCCGCGACGATGCCCCTCAACGTTAGCTTCACCAACAGGAACTATGACCTCGACTACGACTCGGTGCAGCCGTATTTCTACTGCGACGAGGAGGAGAACTTCTACCAGCAGCAGCAGCAGAGCGAGCT-113-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GCAGCCCCCGGCGCCCAGCGAGGATATCTGGAAGAAATTCGAGCTGCTGCCCACCCCGCCCCTGTCCCCTAGCCGCCGCTCCGGGCTCTGCTCGCCCTCCTACGTTGCGGTCACACCCTTCTCCCTTCGGGGAGACAACGACGGCGGTGGCGGGAGCTTCTCCACGGCCGACCAGCTGGAGATGGTGACCGAGCTGCTGGGAGGAGACATGGTGAACCAGAGTTTCATCTGCGACCCGGACGACGAGACCTTCATCAAAAACATCATCATCCAGGACTGTATGTGGAGCGGCTTCTCGGCCGCCGCCAAGCTCGTCTCAGAGAAGCTGGCCTCCTACCAGGCTGCGCGCAAAGACAGCGGCAGCCCGAACCCCGCCCGCGGCCACAGCGTCTGCTCCACCTCCAGCTTGTACCTGCAGGATCTGAGCGCCGCCGCCTCAGAGTGCATCGACCCCTCGGTGGTCTTCCCCTACCCTCTCAACGACAGCAGCTCGCCCAAGTCCTGCGCCTCGCAAGACTCCAGCGCCTTCTCTCCGTCCTCGGATTCTCTGCTCTCCTCGACGGAGTCCTCCCCGCAGGGCAGCCCCGAGCCCCTGGTGCTCCATGAGGAGACACCGCCCACCACCAGCAGCGACTCTGAGGAGGAACAAGAAGATGAGGAAGAAATCGATGTTGTTTCTGTGGAAAAGAGGCAGGCTCCTGGCAAAAGGTCAGAGTCTGGATCACCTTCTGCTGGAGGCCACAGCAAACCTCCTCACAGCCCACTGGTCCTCAAGAGGTGCCACGTCTCCACACATCAGCACAACTACGCAGCGCCTCCCTCCACTCGGAAGGACTATCCTGCTGCCAAGAGGGTCAAGTTGGACAGTGTCAGAGTCCTGAGACAGATCAGCAACAACCGAAAATGCACCAGCCCCAGGTCCTCGGACACCGAGGAGAATGTCAAGAGGCGAACACACAACGTCTTGGAGCGCCAGAGGAGGAACGAGCTAAAACGGAGCTTTTTTGCCCTGCGTGACCAGATCCCGGAGTTGGAAAACAATGAAAAGGCCCCCAAGGTAGTTATCCTTAAAAAAGCCACAGCATACATCCTGTCCGTCCAAGCAGAGGAGCAAAAGCTCATTTCTGAAGAGGACTTGTTGCGGAAACGACGAGAACAGTTGAAACACAAACTTGAACAGCTACGGAACTCTTGTGCG> SEQ ID NO: 22> PIK3CD E1021K ; Length: 3132 nucleotidesATGCCCCCTGGGGTGGACTGCCCCATGGAATTCTGGACCAAGGAGGAGAATCAGAGCGTTGTGGTTGACTTCCTGCTGCCCACAGGGGTCTACCTGAACTTCCCTGTGTCCCGCAATGCCAACCTCAGCACCATCAAGCAGCTGCTGTGGCACCGCGCCCAGTATGAGCCGCTCTTCCACATGCTCAGTGGCCCCGAGGCCTATGTGTTCACCTGCATCAACCAGACAGCGGAGCAGCAAGAGCTGGAGGACGAGCAACGGCGTCTGTGTGACGTGCAGCCCTTCCTGCCCGTCCTGCGCCTGGTGGCCCGTGAGGGCGACCGCGTGAAGAAGCTCATCAACTCACAGATCAGCCTCCTCATCGGCAAAGGCCTCCACGAGTTTGACTCCTTGTGCGACCCAGAAGTGAACGACTTTCGCGCCAAGATGTGCCAATTCTGCGAGGAGGCGGCCGCCCGCCGGCAGCAGCTGGGCTGGGAGGCCTGGCTGCAGTACAGTTTCCCCCTGCAGCTGGAGCCCTCGGCTCAAACCTGGGGGCCTGGTACCCTGCGGCTCCCGAACCGGGCCCTTCTGGTCAACGTTAAGTTTGAGGGCAGCGAGGAGAGCTTCACCTTCCAGGTGTCCACCAAGGACGTGCCGCTGGCGCTGATGGCCTGTGCCCTGCGGAAGAAGGCCACAGTGTTCCGGCAGCCGCTGGTGGAGCAGCCGGAAGACTACACGCTGCAGGTGAACGGCAGGCATGAGTACCTGTATGGCAGCTACCCGCTCTGCCAGTTCCAGTACATCTGCAGCTGCCTGCACAGTGGGTTGACCCCTCACCTGACCATGGTCCATTCCTCCTCCATCCTCGCCATGCGGGATGAGCAGAGCAACCCTGCCCCCCAGGTCCAGAAACCGCGTGCCAAACCACCTCCCATTCCTGCGAAGAAGCCTTCCTCTGTGTCCCTGTGGTCCCTGGAGCAGCCGTTCCGCATCGAGCTCATCCAGGG-114-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CAGCAAAGTGAACGCCGACGAGCGGATGAAGCTGGTGGTGCAGGCCGGGCTTTTCCACGGCAACGAGATGCTGTGCAAGACGGTGTCCAGCTCGGAGGTGAGCGTGTGCTCGGAGCCCGTGTGGAAGCAGCGGCTGGAGTTCGACATCAACATCTGCGACCTGCCCCGCATGGCCCGTCTCTGCTTTGCGCTGTACGCCGTGATCGAGAAAGCCAAGAAGGCTCGCTCCACCAAGAAGAAGTCCAAGAAGGCGGACTGCCCCATTGCCTGGGCCAACCTCATGCTGTTTGACTACAAGGACCAGCTTAAGACCGGGGAACGCTGCCTCTACATGTGGCCCTCCGTCCCAGATGAGAAGGGCGAGCTGCTGAACCCCACGGGCACTGTGCGCAGTAACCCCAACACGGATAGCGCCGCTGCCCTGCTCATCTGCCTGCCCGAGGTGGCCCCGCACCCCGTGTACTACCCCGCCCTGGAGAAGATCTTGGAGCTGGGGCGACACAGCGAGTGTGTGCATGTCACCGAGGAGGAGCAGCTGCAGCTGCGGGAAATCCTGGAGCGGCGGGGGTCTGGGGAGCTGTATGAGCACGAGAAGGACCTGGTGTGGAAGCTGCGGCATGAAGTCCAGGAGCACTTCCCGGAGGCGCTAGCCCGGCTGCTGCTGGTCACCAAGTGGAACAAGCATGAGGATGTGGCCCAGATGCTCTACCTGCTGTGCTCCTGGCCGGAGCTGCCCGTCCTGAGCGCCCTGGAGCTGCTAGACTTCAGCTTCCCCGATTGCCACGTAGGCTCCTTCGCCATCAAGTCGCTGCGGAAACTGACGGACGATGAGCTGTTCCAGTACCTGCTGCAGCTGGTGCAGGTGCTCAAGTACGAGTCCTACCTGGACTGCGAGCTGACCAAATTCCTGCTGGACCGGGCCCTGGCCAACCGCAAGATCGGCCACTTCCTTTTCTGGCACCTCCGCTCCGAGATGCACGTGCCGTCGGTGGCCCTGCGCTTCGGCCTCATCCTGGAGGCCTACTGCAGGGGCAGCACCCACCACATGAAGGTGCTGATGAAGCAGGGGGAAGCACTGAGCAAACTGAAGGCCCTGAATGACTTCGTCAAGCTGAGCTCTCAGAAGACCCCCAAGCCCCAGACCAAGGAGCTGATGCACTTGTGCATGCGGCAGGAGGCCTACCTAGAGGCCCTCTCCCACCTGCAGTCCCCACTCGACCCCAGCACCCTGCTGGCTGAAGTCTGCGTGGAGCAGTGCACCTTCATGGACTCCAAGATGAAGCCCCTGTGGATCATGTACAGCAACGAGGAGGCAGGCAGCGGCGGCAGCGTGGGCATCATCTTTAAGAACGGGGATGACCTCCGGCAGGACATGCTGACCCTGCAGATGATCCAGCTCATGGACGTCCTGTGGAAGCAGGAGGGGCTGGACCTGAGGATGACCCCCTATGGCTGCCTCCCCACCGGGGACCGCACAGGCCTCATTGAGGTGGTACTCCGTTCAGACACCATCGCCAACATCCAACTCAACAAGAGCAACATGGCAGCCACAGCCGCCTTCAACAAGGATGCCCTGCTCAACTGGCTGAAGTCCAAGAACCCGGGGGAGGCCCTGGATCGAGCCATTGAGGAGTTCACCCTCTCCTGTGCTGGCTATTGTGTGGCCACATATGTGCTGGGCATTGGCGATCGGCACAGCGACAACATCATGATCCGAGAGAGTGGGCAGCTGTTCCACATTGATTTTGGCCACTTTCTGGGGAATTTCAAGACCAAGTTTGGAATCAACCGCGAGCGTGTCCCATTCATCCTCACCTACGACTTTGTCCATGTGATTCAGCAGGGGAAGACTAATAATAGTGAGAAATTTGAACGGTTCCGGGGCTACTGTGAAAGGGCCTACACCATCCTGCGGCGCCACGGGCTTCTCTTCCTCCACCTCTTTGCCCTGATGCGGGCGGCAGGCCTGCCTGAGCTCAGCTGCTCCAAAGACATCCAGTATCTCAAGGACTCCCTGGCACTGGGGAAAACAGAGGAGGAGGCACTGAAGCACTTCCGAGTGAAGTTTAACAAAGCCCTCCGTGAGAGCTGGAAAACCAAAGTGAACTGGCTGGCCCACAACGTGTCCAAAGACAACAGGCAG> SEQ ID NO: 23> PIM2 A27V ; Length: 933 nucleotides4919-8127-7289.1Atty. Dkt. No.: 121384-0284ATGTTGACCAAGCCTCTACAGGGGCCTCCCGCGCCCCCCGGGACCCCCACGCCGCCGCCAGGAGGCAAGGATCGGGAAGTGTTCGAGGCCGAGTATCGACTCGGCCCCCTCCTGGGTAAGGGGGGCTTTGGCACCGTCTTCGCAGGACACCGCCTCACAGATCGACTCCAGGTGGCCATCAAAGTGATTCCCCGGAATCGTGTGCTGGGCTGGTCCCCCTTGTCAGACTCAGTCACATGCCCACTCGAAGTCGCACTGCTATGGAAAGTGGGTGCAGGTGGTGGGCACCCTGGCGTGATCCGCCTGCTTGACTGGTTTGAGACACAGGAGGGCTTCATGCTGGTCCTCGAGCGGCCTTTGCCCGCCCAGGATCTCTTTGACTATATCACAGAGAAGGGCCCACTGGGTGAAGGCCCAAGCCGCTGCTTCTTTGGCCAAGTAGTGGCAGCCATCCAGCACTGCCATTCCCGTGGAGTTGTCCATCGTGACATCAAGGATGAGAACATCCTGATAGACCTACGCCGTGGCTGTGCCAAACTCATTGATTTTGGTTCTGGTGCCCTGCTTCATGATGAACCCTACACTGACTTTGATGGGACAAGGGTGTACAGCCCCCCAGAGTGGATCTCTCGACACCAGTACCATGCACTCCCGGCCACTGTCTGGTCACTGGGCATCCTCCTCTATGACATGGTGTGTGGGGACATTCCCTTTGAGAGGGACCAGGAGATTCTGGAAGCTGAGCTCCACTTCCCAGCCCATGTCTCCCCAGACTGCTGTGCCCTAATCCGCCGGTGCCTGGCCCCCAAACCTTCTTCCCGACCCTCACTGGAAGAGATCCTGCTGGACCCCTGGATGCAAACACCAGCCGAGGATGTACCCCTCAACCCCTCCAAAGGAGGCCCTGCCCCTTTGGCCTGGTCCTTGCTACCC> SEQ ID NO: 24 ; MAP2K1 F53Y> Length: 1179 nucleotidesATGCCCAAGAAGAAGCCGACGCCCATCCAGCTGAACCCGGCCCCCGACGGCTCT GCAGTTAACGGGACCAGCTCTGCGGAGACCAACTTGGAGGCCTTGCAGAAGAAG CTGGAGGAGCTAGAGCTTGATGAGCAGCAGCGAAAGCGCCTTGAGGCCTATCTTA CCCAGAAGCAGAAGGTGGGAGAACTGAAGGATGACGACTTTGAGAAGATCAGTG AGCTGGGGGCTGGCAATGGCGGTGTGGTGTTCAAGGTCTCCCACAAGCCTTCTGG CCTGGTCATGGCCAGAAAGCTAATTCATCTGGAGATCAAACCCGCAATCCGGAAC CAGATCATAAGGGAGCTGCAGGTTCTGCATGAGTGCAACTCTCCGTACATCGTGG GCTTCTATGGTGCGTTCTACAGCGATGGCGAGATCAGTATCTGCATGGAGCACATG GATGGAGGTTCTCTGGATCAAGTCCTGAAGAAAGCTGGAAGAATTCCTGAACAAA TTTTAGGAAAAGTTAGCATTGCTGTAATAAAAGGCCTGACATATCTGAGGGAGAAGCACAAGATCATGCACAGAGATGTCAAGCCCTCCAACATCCTAGTCAACTCCCGTG GGGAGATCAAGCTCTGTGACTTTGGGGTCAGCGGGCAGCTCATCGACTCCATGGC CAACTCCTTCGTGGGCACAAGGTCCTACATGTCGCCAGAAAGACTCCAGGGGACT CATTACTCTGTGCAGTCAGACATCTGGAGCATGGGACTGTCTCTGGTAGAGATGGC GGTTGGGAGGTATCCCATCCCTCCTCCAGATGCCAAGGAGCTGGAGCTGATGTTTG GGTGCCAGGTGGAAGGAGATGCGGCTGAGACCCCACCCAGGCCAAGGACCCCCG GGAGGCCCCTTAGCTCATACGGAATGGACAGCCGACCTCCCATGGCAATTTTTGAG TTGTTGGATTACATAGTCAACGAGCCTCCTCCAAAACTGCCCAGTGGAGTGTTCAG TCTGGAATTTCAAGATTTTGTGAATAAATGCTTAATAAAAAACCCCGCAGAGAGAG CAGATTTGAAGCAACTCATGGTTCATGCTTTTATCAAGAGATCTGATGCTGAGGAA GTGGATTTTGCAGGTTGGCTCTGCTCCACCATCGGCCTTAACCAGCCCAGCACACC AACCCATGCTGCTGGCGTC-116-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> SEQ ID NO: 25> OSBPLIO R94K ; Length: 2292 nucleotidesATGGAGAGGGCAGTCCAGGGCACAGACGGCGGCGGGGGTAGCAACAGCAGCAGCCGCAGCAGCAGCCGTGCTACCTCGGCGGGCTCCTCGCCCTCCTGCTCTCTGGCGGGCCGGGGGGTCTCCAGCCGGTCGGCGGCGGCCGGGCTCGGCGGCGGGGGAAGCCGCAGCAGCCCGGGCTCTGTGGCCGCTAGCCCGTCCGGGGGAGGCGGCCGCAGGAGGGAGCCGGCGCTCGAGGGCGTGCTCAGCAAATACACCAACCTCCTCCAGGGCTGGCAGAACAAGTACTTCGTACTGGATTTCGAGGCTGGCATCCTGCAGTATTTTGTGAATGAGCAAAGCAAACACCAGAAGCCTCGAGGAGTCCTGTCTTTATCTGGAGCCATAGTGTCCCTGAGCGATGAAGCTCCCCACATGCTGGTGGTGTACTCTGCTAATGGAGAGATGTTTAAACTGAGAGCTGCTGATGCAAAAGAGAAACAATTCTGGGTGACTCAGCTTCGAGCTTGTGCCAAATACCACATGGAAATGAATTCTAAGAGTGCTCCAAGCTCCCGAAGCCGAAGTCTCACTTTGCTCCCACATGGAACACCCAATTCTGCGTCTCCCTGTAGCCAGAGACACCTCAGTGTGGGGGCCCCCGGTGTTGTCACAATCACGCATCACAAGTCGCCTGCAGCCGCCCGAAGAGCCAAGAGTCAGTATTCCGGCCAGCTTCACGAAGTCAGAGAGATGATGAACCAGGTGGAAGGGCAGCAGAAGAACCTTGTGCACGCCATTGAGTCCCTGCCAGGGTCCGGCCCCCTCACTGCCTTGGACCAGGACCTGCTGCTCCTGAAAGCTACCTCTGCTGCCACCCTCAGCTGCCTTGGGGAGTGCCTCAACTTGTTACAGCAGAGTGTGCACCAGGCGGGCCAGCCCAGCCAGAAGCCAGGAGCCTCGGAAAACATCCTGGGATGGCACGGGTCCAAGTCACATTCCACAGAGCAGCTGAAAAATGGGACACTTGGCTCTTTGCCATCAGCCAGTGCCAACATAACCTGGGCAATTTTACCAAACTCTGCTGAAGACGAACAAACCTCACAGCCAGAGCCAGAGCCAAACTCAGGCTCTGAATTGGTTTTGTCTGAAGATGAAAAAAGTGACAATGAAGATAAGGAAGAGACGGAATTGGGCGTCATGGAGGATCAGCGTAGTATAATTCTTCATCTCATTTCACAACTCAAACTTGGAATGGATTTGACCAAGGTGGTGCTTCCCACCTTTATCCTGGAGAAGCGATCTTTGCTGGAGATGTATGCAGATTTCATGGCGCACCCAGACCTACTGCTGGCCATCACCGCTGGGGCCACACCAGAGGAGAGAGTCATTTGCTTCGTTGAGTATTATCTCACAGCCTTTCACGAGGGCCGCAAGGGCGCTTTAGCCAAGAAGCCCTACAACCCCATCATAGGCGAGACATTTCACTGCTCCTGGGAAGTTCCCAAGGACAGGGTCAAGCCTAAGAGGACTGCTTCCCGCTCTCCTGCCAGCTGTCACGAACACCCAATGGCCGATGACCCTTCCAAAAGCTACAAACTAAGGTTTGTGGCTGAGCAAGTGTCCCATCACCCACCCATCTCCTGCTTCTACTGTGAGTGCGAGGAGAAGAGACTGTGCGTCAACACTCATGTATGGACCAAAAGCAAGTTCATGGGCATGTCCGTGGGGGTCTCTATGATAGGGGAAGGTGTGTTGAGGCTCCTGGAACACGGGGAGGAGTACGTATTCACCCTGCCTAGTGCCTACGCCCGGTCCATTCTCACCATCCCGTGGGTGGAGCTCGGAGGAAAAGTCAGCATCAACTGTGCCAAGACTGGGTACTCAGCGACAGTGATATTCCACACGAAGCCTTTCTATGGAGGGAAAGTCCACAGGGTTACCGCAGAAGTGAAGCACAACCCAACCAACACCATTGTTTGTAAAGCCCATGGGGAATGGAATGGTACTTTAGAGTTCACCTACAACAATGGAGAAACCAAAGTCATCGACACAACCACACTGCCAGTGTATCCCAAGAAGATCAGACCTCTTGAGAAGCAGGGACCCATGGAGTCCAGGAACCTCTGGCGGGAGGTGACCCGATACCTGCGGCTGGGGGACATTGACGCAGCCACCGAGCAGAAGCGGCACCTGGAGGAGAAGCAACGGGTGGAGGAACGGAAGCGCGAGAACCTCCGCACACCATGGAAGCCCAAATATTTTATCCAGGAGGGCGATGGCTGGGTATACTTCAATCCCCTCTGGAAAGCACAC-117-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> SEQ ID NO: 26> FOXP1 wild-type; Length: 2082 nucleotidesATGATGCAAGAATCTGGGACTGAGACAAAAAGTAACGGTTCAGCCATCCAGAATGGGTCGGGCGGCAGCAACCACTTACTAGAGTGCGGCGGTCTTCGGGAGGGGCGGTCCAACGGAGAGACGCCGGCCGTGGACATCGGGGCAGCTGACCTCGCCCACGCCCAGCAGCAGCAGCAACAGGCACTTCAGGTGGCAAGACAGCTCCTTCTTCAGCAGCAACAGCAGCAGCAAGTTAGTGGATTAAAATCTCCCAAGAGGAATGACAAACAAC CAGCTCTTCAGGTTCCCGTGTCAGTGGCTATGATGACACCTCAAGTTATCACTCCC CAGCAAATGCAGCAGATCCTCCAGCAACAAGTGCTGAGCCCTCAGCAGCTCCAG GTTCTCCTCCAGCAGCAGCAGGCCCTCATGCTTCAACAGCAGCAGCTTCAAGAGTTTTATAAAAAACAACAGGAACAGTTGCAGCTTCAACTTTTACAACAACAACATGCTGGAAAACAGCCTAAAGAGCAACAGCAGGTGGCTACCCAGCAGTTGGCTTTTCAGCAGCAGCTTTTACAGATGCAGCAGTTACAGCAGCAGCACCTCCTGTCTTTGCAG CGCCAAGGCCTTCTGACAATTCAGCCCGGGCAGCCTGCCCTTCCCCTTCAACCTCT TGCTCAAGGCATGATTCCAACAGAACTGCAGCAGCTCTGGAAAGAAGTGACAAG TGCTCATACTGCAGAAGAAACCACAGGCAACAATCACAGCAGTTTGGATCTGACCACGACATGTGTCTCCTCCTCTGCACCTTCCAAGACCTCCTTAATAATGAACCCACATGCCTCTACCAATGGACAGCTCTCAGTCCACACTCCCAAAAGGGAAAGTTTGTCCCATGAGGAGCACCCCCATAGCCATCCTCTCTATGGACATGGTGTATGCAAGTGGCCAGGCTGTGAAGCAGTGTGCGAAGATTTCCAATCATTTCTAAAACATCTCAACAGTGAGCATGCGCTGGACGATAGAAGTACAGCCCAATGTAGAGTACAAATGCAGGTTGTACAGCAGTTAGAGCTACAGCTTGCAAAAGACAAAGAACGCCTGCAAGCCATGATGACCCACCTGCATGTGAAGTCTACAGAACCCAAAGCCGCCCCTCAGCCCTTGAATCTGGTATCAAGTGTCACTCTCTCCAAGTCCGCATCGGAGGCTTCTCCACAGAGCTTACCTCATACTCCAACGACCCCAACCGCCCCCCTGACTCCCGTCACCCAAGGCCCCTCTGTCATCACAACCACCAGCATGCACACGGTGGGACCCATCCGCAGGCGGTACTCAGACAAATACAACGTGCCCATTTCGTCAGCAGATATTGCGCAGAACCAAGAATTTTATAAGAACGCAGAAGTTAGACCACCATTTACATATGCATCTTTAATTAGGCAGGCCATTCTCGAATCTCCAGAAAAGCAGCTAACACTAAATGAGATCTATAACTGGTTCACACGAATGTTTGCTTACTTCCGACGCAACGCGGCCACGTGGAAGGGTGCCATTCGC ACCAACCTCTCACTGCATAAGTGCTTTATCAGAGTAGAGGATGAGTTTGGGTCCTT TTGGACAGTTGATGATGAAGAGTTTAAACGTGGCCGCCATATTCAACGAGGCCGT CCTCGCAAATACTGCCCCGATGAAAACTTTGACGAGCTTGTCGCACATAACCCTTCCCTTATTAAAAACATGCAGAGCAGCCACGCCTACTGCACACCTCTCAATGCAGCTT TACAGGCTTCAATGGCTGAGAATAGTATACCTCTATACACTACCGCTTCCATGGGAA ATCCCACTCTGGGCAACTTAGCCAGCGCAATACGGGAAGAGCTGAACGGGGCAAT GGAGCATACCAACAGCAACGAGAGTGACAGCAGTCCAGGCAGATCTCCTATGCAAGCCGTGCATCCTGTACACGTCAAAGAAGAGCCCCTCGATCCAGAGGAAGCTGAA GGGCCCCTGTCCTTAGTGACAACAGCCAACCACAGTCCAGATTTTGACCATGACA GAGATTACGAAGATGAACCAGTAAACGAGGACATGGAGTGA> SEQ ID NO: 27-118-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> TNFRSF14 C135S ; Length: 579 nucleotidesATGGAGCCTCCTGGAGACTGGGGGCCTCCTCCCTGGAGATCCACCCCCAAAACCGACGTCTTGAGGCTGGTGCTGTATCTCACCTTCCTGGGAGCCCCCTGCTACGCCCCAGCTCTGCCGTCCTGCAAGGAGGACGAGTACCCAGTGGGCTCCGAGTGCTGCCCCAAGTGCAGTCCAGGTTATCGTGTGAAGGAGGCCTGCGGGGAGCTGACGGGCACAGTGTGTGAACCCTGCCCTCCAGGCACCTACATTGCCCACCTCAATGGCCTAAGCAAGTGTCTGCAGTGCCAAATGTGTGACCCAGCCATGGGCCTGCGCGCGAGCCGGAACTGCTCCAGGACAGAGAACGCCGTGTGTGGCTGCAGCCCAGGCCACTTCTGCATCGTCCAGGACGGGGACCACAGCGCCGCGTGCCGCGCTTACGCCACCTCCAGCCCGGGCCAGAGGGTGCAGAAGGGAGGCACCGAGAGTCAGGACACCCTGTGTCAGAACTGCCCCCCGGGGACCTTCTCTCCCAATGGGACCCTGGAGGAATGTCAGCACCAGACCAACCGAGCTTGGAAAAGTCAGACAGACCTC> SEQ ID NO: 28> CD79B Y196F ; Length: 687 nucleotidesATGGCCAGGCTGGCGTTGTCTCCTGTGCCCAGCCACTGGATGGTGGCGTTGCTGCTGCTGCTCTCAGCTGAGCCAGTACCAGCAGCCAGATCGGAGGACCGGTACCGGAATCCCAAAGGTAGTGCTTGTTCGCGGATCTGGCAGAGCCCACGTTTCATAGCCAGGAAACGGGGCTTCACGGTGAAAATGCACTGCTACATGAACAGCGCCTCCGGCAATGTGAGCTGGCTCTGGAAGCAGGAGATGGACGAGAATCCCCAGCAGCTGAAGCTGGAAAAGGGCCGCATGGAAGAGTCCCAGAACGAATCTCTCGCCACCCTCACCATCCAAGGCATCCGGTTTGAGGACAATGGCATCTACTTCTGTCAGCAGAAGTGCAACAACACCTCGGAGGTCTACCAGGGCTGCGGCACAGAGCTGCGAGTCATGGGATTCAGCACCTTGGCACAGCTGAAGCAGAGGAACACGCTGAAGGATGGTATCATCATGATCCAGACGCTGCTGATCATCCTCTTCATCATCGTGCCTATCTTCCTGCTGCTGGACAAGGATGACAGCAAGGCTGGCATGGAGGAAGATCACACCTTCGAGGGCCTGGACATTGACCAGACAGCCACCTATGAGGACATAGTGACGCTGCGGACAGGGGAAGTGAAGTGGTCTGTAGGTGAGCACCCAGGCCAGGAG> SEQ ID NO: 29> HIST1H2BC M63I ; Length: 378 nucleotidesATGCCTGAGCCAGCCAAGTCTGCTCCCGCCCCGAAGAAGGGCTCCAAGAAGGCAGTGACCAAAGCGCAGAAGAAAGATGGCAAGAAGCGCAAGCGCAGCCGCAAGGAGAGTTACTCTGTGTACGTGTACAAGGTGCTGAAACAGGTCCATCCCGACACTGGCATCTCTTCCAAGGCCATGGGCATCATAAATTCTTTCGTTAACGACATATTTGAGCGCATCGCGGGCGAGGCTTCCCGCCTGGCGCATTACAACAAGCGCTCGACCATCACCTCCAGGGAGATCCAGACGGCCGTGCGCCTGCTGCTTCCCGGAGAGCTGGCCAAGCACGCCGTGTCGGAGGGCACCAAGGCCGTCACCAAGTACACCAGCTCCAAG-119-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> SEQ ID NO: 30> STAT6 D419G ; Length: 2541 nucleotidesATGTCTCTGTGGGGTCTGGTCTCCAAGATGCCCCCAGAAAAAGTGCAGCGGCTCTATGTCGACTTTCCCCAACACCTGCGGCATCTTCTGGGTGACTGGCTGGAGAGCCAGCCCTGGGAGTTCCTGGTCGGCTCCGACGCCTTCTGCTGCAACTTGGCTAGTGCCCTACTTTCAGACACTGTCCAGCACCTTCAGGCCTCGGTGGGAGAGCAGGGGGAGGGGAGCACCATCTTGCAACACATCAGCACCCTTGAGAGCATATATCAGAGGGACCCCCTGAAGCTGGTGGCCACTTTCAGACAAATACTTCAAGGAGAGAAAAAAGCTGTTATGGAACAGTTCCGCCACTTGCCAATGCCTTTCCACTGGAAGCAGGAAGAACTCAAGTTTAAGACAGGCTTGCGGAGGCTGCAGCACCGAGTAGGGGAGATCCACCTTCTCCGAGAAGCCCTGCAGAAGGGGGCTGAGGCTGGCCAAGTGTCTCTGCACAGCTTGATAGAAACTCCTGCTAATGGGACTGGGCCAAGTGAGGCCCTGGCCATGCTACTGCAGGAGACCACTGGAGAGCTAGAGGCAGCCAAAGCCCTAGTGCTGAAGAGGATCCAGATTTGGAAACGGCAGCAGCAGCTGGCAGGGAATGGCGCACCGTTTGAGGAGAGCCTGGCCCCACTCCAGGAGAGGTGTGAAAGCCTGGTGGACATTTATTCCCAGCTACAGCAGGAGGTAGGGGCGGCTGGTGGGGAGCTTGAGCCCAAGACCCGGGCATCGCTGACTGGCCGGCTGGATGAAGTCCTGAGAACCCTCGTCACCAGTTGCTTCCTGGTGGAGAAGCAGCCCCCCCAGGTACTGAAGACTCAGACCAAGTTCCAGGCTGGAGTTCGATTCCTGTTGGGCTTGAGGTTCCTGGGGGCCCCAGCCAAGCCTCCGCTGGTCAGGGCCGACATGGTGACAGAGAAGCAGGCGCGGGAGCTGAGTGTGCCTCAGGGTCCTGGGGCTGGAGCAGAAAGCACTGGAGAAATCATCAACAACACTGTGCCCTTGGAGAACAGCATTCCTGGGAACTGCTGCTCTGCCCTGTTCAAGAACCTGCTTCTCAAGAAGATCAAGCGGTGTGAGCGGAAGGGCACTGAGTCTGTCACAGAGGAGAAGTGCGCTGTGCTCTTCTCTGCCAGCTTCACACTTGGCCCCGGCAAACTCCCCATCCAGCTCCAGGCCCTGTCTCTGCCCCTGGTGGTCATCGTCCATGGCAACCAAGGCAACAATGCCAAAGCCACTATCCTGTGGGACAATGCCTTCTCTGAGATGGACCGCGTGCCCTTTGTGGTGGCTGAGCGGGTGCCCTGGGAGAAGATGTGTGAAACTCTGAACCTGAAGTTCATGGCTGAGGTGGGGACCAACCGGGGGCTGCTCCCAGAGCACTTCCTCTTCCTGGCCCAGAAGATCTTCAATGACAACAGCCTCAGTATGGAGGCCTTCCAGCACCGTTCTGTGTCCTGGTCGCAGTTCAACAAGGAGATCCTGCTGGGCCGTGGCTTCACCTTTTGGCAGTGGTTTGATGGTGTCCTGGACCTCACCAAACGCTGTCTCCGGAGCTACTGGTCTGACCGGCTGATCATTGGCTTCATCAGCAAACAGTACGTTACTAGCCTTCTTCTCAATGAGCCCGACGGAACCTTTCTCCTCCGCTTCAGCGACTCAGAGATTGGGGGCATCACCATTGCCCATGTCATCCGGGGCCAGGATGGCTCTCCACAGATAGAGAACATCCAGCCATTCTCTGCCAAAGACCTGTCCATTCGCTCACTGGGGGACCGAATCCGGGATCTTGCTCAGCTCAAAAATCTCTATCCCAAGAAGCCCAAGGATGAGGCTTTCCGGAGCCACTACAAGCCTGAACAGATGGGTAAGGATGGCAGGGGTTATGTCCCAGCTACCATCAAGATGACCGTGGAAAGGGACCAACCACTTCCTACCCCAGAGCTCCAGATGCCTACCATGGTGCCTTCTTATGACCTTGGAATGGCCCCTGATTCCTCCATGAGCATGCAGCTTGGCCCAGATATGGTGCCCCAGGTGTACCCACCACACTCTCACTCCATCCCCCCGTATCAAGGCCTCTCCCCAGAAGAATCAGTCAACGTGTTGTCAGCCTTCCAGGAGCCTCACCTGCAGATGCCCCCCAGCCTGGGCCAGATGAGCCTGCCCTTTGACCAGCCTCACCCCCAGGGCCTGCTGCCGTGCCAGCCTCAGGAG-120-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CATGCTGTGTCCAGCCCTGACCCCCTGCTCTGCTCAGATGTGACCATGGTGGAAGACAGCTGCCTGAGCCAGCCAGTGACAGCGTTTCCTCAGGGCACTTGGATTGGTGAAGACATATTCCCTCCTCTGCTGCCTCCCACTGAACAGGACCTCACTAAGCTTCTCCTGGAGGGGCAAGGGGAGTCGGGGGGAGGGTCCTTGGGGGCACAGCCCCTCCTGCAGCCCTCCCACTATGGGCAATCTGGGATCTCAATGTCCCACATGGACCTAAGGGCC AACCCCAGTTGGSEQ ID NO: 31SGK1 A143V ; Length: 1578 nucleotidesATGGTAAACAAAGACATGAATGGATTCCCAGTCAAGAAATGCTCAGCCTTCCAATTTTTTAAGAAGCGGGTACGAAGGTGGATCAAGAGCCCAATGGTCAGTGTGGACAAGCATCAGAGTCCCAGCCTGAAGTACACCGGCTCCTCCATGGTGCACATCCCTCCAGGGGAGCCAGACTTCGAGTCTTCCTTGTGTCAAACATGCCTGGGTGAACATGCTTTCCAAAGAGGGGTTCTCCCTCAGGAGAACGAGTCATGTTCATGGGAAACTCAATCTGGGTGTGAAGTGAGAGAGCCATGTAATCATGCCAACATCCTGACCAAGCCCGATCCAAGAACCTTCTGGACTAATGATGATCCAGCTTTCATGAAGCAGAGGAGGATGGGTCTGAACGACTTTATTCAGAAGATTGCCAATAACTCCTATGTATGCAAACACCCTGAAGTTCAGTCCATCTTGAAGATCTCCCAACCTCAGGAGCCTGAGCTTATGAATGCCAACCCTTCTCCTCCACCAAGTCCTTCTCAGCAAATCAACCTTGGCCCGTCGTCCAATCCTCATGCTAAACCATCTGACTTTCACTTCTTGAAAGTGATCGGAAAGGGCAGTTTTGGAAAGGTTCTTCTAGCAAGACACAAGGCAGAAGAAGTGTTCTATGCAGTCAAAGTTTTACAGAAGAAAGCAATCCTGAAAAAGAAAGAGGAGAAGCATATTATGTCGGAGCGGAATGTTCTGTTGAAGAATGTGAAGCACCCTTTCCTGGTGGGCCTTCACTTCTCTTTCCAGACTGCTGACAAATTGTACTTTGTCCTAGACTACATTAATGGTGGAGAGTTGTTCTACCATCTCCAGAGGGAACGCTGCTTCCTGGAACCACGGGCTCGTTTCTATGCTGCTGAAATAGCCAGTGCCTTGGGCTACCTGCATTCACTGAACATCGTTTATAGAGACTTAAAACCAGAGAATATTTTGCTAGATTCACAGGGACACATTGTCCTTACTGACTTCGGACTCTGCAAGGAGAACATTGAACACAACAGCACAACATCCACCTTCTGTGGCACGCCGGAGTATCTCGCACCTGAGGTGCTTCATAAGCAGCCTTATGACAGGACTGTGGACTGGTGGTGCCTGGGAGCTGTCTTGTATGAGATGCTGTATGGCCTGCCGCCTTTTTATAGCCGAAACACAGCTGAAATGTACGACAACATTCTGAACAAGCCTCTCCAGCTGAAACCAAATATTACAAATTCCGCAAGACACCTCCTGGAGGGCCTCCTGCAGAAGGACAGGACAAAGCGGCTCGGGGCCAAGGATGACTTCATGGAGATTAAGAGTCATGTCTTCTTCTCCTTAATTAACTGGGATGATCTCATTAATAAGAAGATTACTCCCCCTTTTAACCCAAATGTGAGTGGGCCCAACGACCTACGGCACTTTGACCCCGAGTTTACCGAAGAGCCTGTCCCCAACTCCATTGGCAAGTCCCCTGACAGCGTCCTCGTCACAGCCAGCGTCAAGGAAGCTGCCGAGGCTTTCCTAGGCTTTTCCTATGCGCCTCCCACGGACTCTTTCCTC> SEQ ID NO: 32> RRAGC T90N ; Length: 1197 nucleotides-121-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ATGTCCCTGCAGTACGGGGCGGAGGAGACGCCCCTCGCCGGCAGTTACGGCGCG GCCGATTCGTTTCCAAAGGACTTCGGCTACGGCGTGGAGGAGGAGGAAGAGGAG GCGGCGGCGGCGGGCGGAGGGGTTGGGGCAGGGGCAGGCGGTGGCTGTGGTCC GGGGGGCGCTGACAGCTCCAAGCCGAGGATTCTGCTCATGGGACTCCGGCGCAG CGGCAAGTCCTCCATCCAGAAGGTGGTGTTTCATAAGATGTCACCCAACGAGAAC CTCTTTTTGGAAAGTACCAACAAGATTTATAAGGATGACATTTCCAATAGCTCCTTTGTGAATTTCCAGATATGGGATTTTCCTGGGCAAATGGACTTTTTTGACCCAACCTTT GACTATGAGATGATCTTCAGGGGAACAGGAGCATTGATATACGTCATTGACGCACA GGATGACTACATGGAGGCTTTAACAAGACTTCACATTACTGTTTCTAAAGCCTACA AAGTTAACCCAGACATGAATTTTGAGGTTTTTATTCACAAAGTTGATGGTCTGTCT GATGATCACAAAATAGAAACACAGAGGGACATTCATCAAAGGGCCAATGATGACC TTGCAGATGCTGGGCTAGAAAAACTCCATCTTAGCTTTTATCTGACTAGTATCTATGACCATTCAATATTTGAAGCCTTTAGTAAGGTGGTGCAGAAACTCATTCCACAACTG CCGACCTTGGAAAACCTATTAAATATCTTTATATCAAATTCAGGTATTGAAAAAGCT TTTCTCTTTGATGTTGTCAGCAAAATCTACATTGCAACAGACAGTTCCCCTGTGGA TATGCAATCTTATGAACTTTGCTGTGACATGATCGATGTTGTAATTGATGTGTCTTGT ATATATGGGTTAAAGGAAGATGGAAGTGGAAGTGCTTATGACAAAGAATCTATGGC AATTATCAAGCTGAATAATACAACTGTCCTTTATTTAAAGGAGGTGACTAAATTTTTGGCACTGGTCTGCATTCTAAGGGAAGAAAGCTTTGAAAGAAAAGGTTTAATAGAC TACAACTTCCACTGTTTCCGAAAAGCTATTCATGAGGTTTTTGAGGTGGGTGTGAC TTCTCACAGGAGCTGTGGTCACCAGACTAGTGCCTCCAGTCTGAAAGCGCTGACA CACAATGGCACGCCACGAAACGCCATC> SEQ ID NO: 33> EGR1 K34N ; Length: 1629 nucleotidesATGGCCGCGGCCAAGGCCGAGATGCAGCTGATGTCCCCGCTGCAGATCTCTGACCCGTTCGGATCCTTTCCTCACTCGCCCACCATGGACAACTACCCTAACCTGGAGGAGATGATGCTGCTGAGCAACGGGGCTCCCCAGTTCCTCGGCGCCGCCGGGGCCCCAGAGGGCAGCGGCAGCAACAGCAGCAGCAGCAGCAGCGGGGGCGGTGGAGGCGGCGGGGGCGGCAGCAACAGCAGCAGCAGCAGCAGCACCTTCAACCCTCAGGCGGACACGGGCGAGCAGCCCTACGAGCACCTGACCGCAGAGTCTTTTCCTGACATCTCTCTGAACAACGAGAAGGTGCTGGTGGAGACCAGTTACCCCAGCCAAACCACTCGACTGCCCCCCATCACCTATACTGGCCGCTTTTCCCTGGAGCCTGCACCCAACAGTGGCAACACCTTGTGGCCCGAGCCCCTCTTCAGCTTGGTCAGTGGCCTAGTGAGCATGACCAACCCACCGGCCTCCTCGTCCTCAGCACCATCTCCAGCGGCCTCCTCCGCCTCCGCCTCCCAGAGCCCACCCCTGAGCTGCGCAGTGCCATCCAACGACAGCAGTCCCATTTACTCAGCGGCACCCACCTTCCCCACGCCGAACACTGACATTTTCCCTGAGCCACAAAGCCAGGCCTTCCCGGGCTCGGCAGGGACAGCGCTCCAGTACCCGCCTCCTGCCTACCCTGCCGCCAAGGGTGGCTTCCAGGTTCCCATGATCCCCGACTACCTGTTTCCACAGCAGCAGGGGGATCTGGGCCTGGGCACCCCAGACCAGAAGCCCTTCCAGGGCCTGGAGAGCCGCACCCAGCAGCCTTCGCTAACCCCTCTGTCTACTATTAAGGCCTTTGCCACTCAGTCGGGCTCCCAGGACCTGAAGGCCCTCAATACCAGCTACCAGTCCCAGCTCATCAAACCCAGCCGCATGCGCAAGTACCCCAACCGGCCCAGCAAG-122-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ACGCCCCCCCACGAACGCCCTTACGCTTGCCCAGTGGAGTCCTGTGATCGCCGCTTCTCCCGCTCCGACGAGCTCACCCGCCACATCCGCATCCACACAGGCCAGAAGCCCTTCCAGTGCCGCATCTGCATGCGCAACTTCAGCCGCAGCGACCACCTCACCACCCACATCCGCACCCACACAGGCGAAAAGCCCTTCGCCTGCGACATCTGTGGAAGAAAGTTTGCCAGGAGCGATGAACGCAAGAGGCATACCAAGATCCACTTGCGGCAGAAGGACAAGAAAGCAGACAAAAGTGTTGTGGCCTCTTCGGCCACCTCCTCTCTCTCTTCCTACCCGTCCCCGGTTGCTACCTCTTACCCGTCCCCGGTTACTACCTCTTATCCATCCCCGGCCACCACCTCATACCCATCCCCTGTGCCCACCTCCTTCTCCTCTCCCGGCTCCTCGACCTACCCATCCCCTGTGCACAGTGGCTTCCCCTCCCCGTCGGTGGCCACCACGTACTCCTCTGTTCCCCCTGCTTTCCCGGCCCAGGTCAGCAGCTTCCCTTCCTCAGCTGTCACCAACTCCTTCAGCGCCTCCACAGGGCTTTCGGACATGACAGCAACCTTTTCTCCCAGGACAATTGAAATTTGC> SEQ ID NO: 34> ATP6V1B2 Y371C ; Length: 1533 nucleotidesATGGCGCTGCGGGCGATGCGGGGGATTGTCAACGGGGCCGCACCCGAGCTACCCGTGCCCACCGGTGGGCCGGCGGTGGGAGCTCGGGAGCAGGCGCTGGCAGTCAGTCGGAACTACCTCTCCCAGCCTCGCCTCACATACAAGACAGTATCTGGAGTCAATGGTCCACTAGTGATCTTAGATCATGTTAAGTTTCCCAGGTATGCTGAAATTGTCCATTTGACCTTACCGGATGGCACAAAGAGAAGTGGGCAAGTTCTGGAAGTTAGTGGTTCCAAGGCAGTAGTTCAGGTATTTGAAGGGACTTCAGGTATAGATGCTAAGAAAACGTCCTGTGAGTTTACTGGGGATATTCTCCGAACACCGGTGTCTGAGGATATGCTTGGTCGGGTATTCAATGGATCGGGAAAACCCATTGACAGAGGTCCTGTTGTACTGGCCGAAGACTTCCTTGATATCATGGGTCAGCCAATCAACCCTCAATGTCGAATCTACCCAGAGGAAATGATTCAGACTGGCATTTCGGCCATCGATGGGATGAACAGTATTGCTAGGGGGCAGAAAATTCCTATCTTCTCTGCTGCTGGGCTACCACACAATGAGATTGCAGCTCAGATCTGTCGCCAGGCTGGTTTGGTAAAGAAATCCAAAGATGTAGTAGACTACAGTGAGGAAAATTTTGCAATTGTATTTGCTGCTATGGGTGTAAACATGGAAACTGCCCGGTTCTTCAAATCTGACTTTGAAGAAAATGGCTCAATGGACAATGTCTGCCTCTTTTTGAACTTGGCTAATGACCCAACCATTGAGCGAATTATCACTCCTCGCCTGGCTCTAACCACAGCTGAATTTCTGGCGTACCAATGTGAGAAACATGTATTGGTTATTCTAACAGACATGAGTTCTTATGCTGAAGCACTTCGAGAGGTTTCAGCAGCCAGGGAAGAGGTACCTGGTCGACGAGGTTTTCCAGGTTACATGTATACAGATTTAGCCACGATATATGAACGCGCTGGGCGAGTGGAAGGGAGAAACGGCTCGATTACTCAAATCCCTATTCTAACCATGCCTAATGATGATATCACTCACCCCATCCCAGACTTGACTGGCTGCATTACAGAGGGGCAGATCTATGTGGACAGACAGCTGCACAACAGACAGATTTATCCACCTATCAATGTGCTGCCCTCACTATCACGGTTAATGAAGTCTGCTATTGGAGAAGGGATGACCAGGAAGGATCATGCCGATGTATCTAACCAGCTATATGCGTGCTATGCTATTGGAAAGGATGTGCAAGCCATGAAAGCTGTCGTTGGAGAAGAAGCCCTTACCTCAGATGATCTTCTCTACTTGGAATTTCTGCAGAAGTTTGAGAGGAACTTCATTGCTCAGGGTCCTTACGAAAATCGCACTGTCTTTGAGACTTTGGACATTGGCTGGCAGCTA CTCCGAATCTTCCCCAAAGAAATGCTGAAGAGAATCCCTCAGAGCACCCTCAGCG AATTTTACCCTCGAGACTCTGCAAAGCAT-123-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> SEQ ID NO: 35> ATP6V1B2 R400Q ; Length: 1533 nucleotidesATGGCGCTGCGGGCGATGCGGGGGATTGTCAACGGGGCCGCACCCGAGCTACCCGTGCCCACCGGTGGGCCGGCGGTGGGAGCTCGGGAGCAGGCGCTGGCAGTCAGTCGGAACTACCTCTCCCAGCCTCGCCTCACATACAAGACAGTATCTGGAGTCAATGGTCCACTAGTGATCTTAGATCATGTTAAGTTTCCCAGGTATGCTGAAATTGTCCATTTGACCTTACCGGATGGCACAAAGAGAAGTGGGCAAGTTCTGGAAGTTAGTGGTTCCAAGGCAGTAGTTCAGGTATTTGAAGGGACTTCAGGTATAGATGCTAAGAAAACGTCCTGTGAGTTTACTGGGGATATTCTCCGAACACCGGTGTCTGAGGATATGCTTGGTCGGGTATTCAATGGATCGGGAAAACCCATTGACAGAGGTCCTGTTGTACTGGCCGAAGACTTCCTTGATATCATGGGTCAGCCAATCAACCCTCAATGTCGAATCTACCCAGAGGAAATGATTCAGACTGGCATTTCGGCCATCGATGGGATGAACAGTATTGCTAGGGGGCAGAAAATTCCTATCTTCTCTGCTGCTGGGCTACCACACAATGAGATTGCAGCTCAGATCTGTCGCCAGGCTGGTTTGGTAAAGAAATCCAAAGATGTAGTAGACTACAGTGAGGAAAATTTTGCAATTGTATTTGCTGCTATGGGTGTAAACATGGAAACTGCCCGGTTCTTCAAATCTGACTTTGAAGAAAATGGCTCAATGGACAATGTCTGCCTCTTTTTGAACTTGGCTAATGACCCAACCATTGAGCGAATTATCACTCCTCGCCTGGCTCTAACCACAGCTGAATTTCTGGCGTACCAATGTGAGAAACATGTATTGGTTATTCTAACAGACATGAGTTCTTATGCTGAAGCACTTCGAGAGGTTTCAGCAGCCAGGGAAGAGGTACCTGGTCGACGAGGTTTTCCAGGTTACATGTATACAGATTTAGCCACGATATATGAACGCGCTGGGCGAGTGGAAGGGAGAAACGGCTCGATTACTCAAATCCCTATTCTAACCATGCCTAATGATGATATCACTCACCCCATCCCAGACTTGACTGGCTACATTACAGAGGGGCAGATCTATGTGGACAGACAGCTGCACAACAGACAGATTTATCCACCTATCAATGTGCTGCCCTCACTATCACAGTTAATGAAGTCTGCTATTGGAGAAGGGATGACCAGGAAGGATCATGCCGATGTATCTAACCAGCTATATGCGTGCTATGCTATTGGAAAGGATGTGCAAGCCATGAAAGCTGTCGTTGGAGAAGAAGCCCTTACCTCAGATGATCTTCTCTACTTGGAATTTCTGCAGAAGTTTGAGAGGAACTTCATTGCTCAGGGTCCTTACGAAAATCGCACTGTCTTTGAGACTTTGGACATTGGCTGGCAGCTA CTCCGAATCTTCCCCAAAGAAATGCTGAAGAGAATCCCTCAGAGCACCCTCAGCG AATTTTACCCTCGAGACTCTGCAAAGCAT> SEQ ID NO: 36> BCL2 WT ; Length: 717 nucleotidesATGGCGCACGCTGGGAGAACAGGGTACGATAACCGGGAGATAGTGATGAAGTACATCCATTATAAGCTGTCGCAGAGGGGCTACGAGTGGGATGCGGGAGATGTGGGCGCCGCGCCCCCGGGGGCCGCCCCCGCACCGGGCATCTTCTCCTCCCAGCCCGGGCACACGCCCCATCCAGCCGCATCCCGGGACCCGGTCGCCAGGACCTCGCCGCTGCAGACCCCGGCTGCCCCCGGCGCCGCCGCGGGGCCTGCGCTCAGCCCGGTGCCACCTGTGGTCCACCTGACCCTCCGCCAGGCCGGCGACGACTTCTCCCGCCGCTACCGCCGCGACTTCGCCGAGATGTCCAGCCAGCTGCACCTGACGCCCTTCACCGCGCGGGGAC-124-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GCTTTGCCACGGTGGTGGAGGAGCTCTTCAGGGACGGGGTGAACTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCATGTGTGTGGAGAGCGTCAACCGGGAGATGTCGCCCCTGGTGGACAACATCGCCCTGTGGATGACTGAGTACCTGAACCGGCACCTGCACACCTGGATCCAGGATAACGGAGGCTGGGATGCCTTTGTGGAACTGTACGGCCCCAGCATGCGGCCTCTGTTTGATTTCTCCTGGCTGTCTCTGAAGACTCTGCTCAGTTTGGCCCTGGTGGGAGCTTGCATCACCCTGGGTGCCTATCTGGGCCACAAG> SEQ ID NO: 37> BTG1 Q36H ; Length: 513 nucleotidesATGCATCCCTTCTACACCCGGGCCGCCACCATGATAGGCGAGATCGCCGCCGCCGTGTCCTTCATCTCCAAGTTTCTCCGCACCAAGGGGCTCACGAGCGAGCGACACCTGCAGACCTTCAGCCAGAGCCTGCAGGAGCTGCTGGCAGAACATTATAAACATCACTGGTTCCCAGAAAAGCCATGCAAGGGATCGGGTTACCGTTGTATTCGCATCAACCATAAAATGGATCCTCTGATTGGACAGGCAGCACAGCGGATTGGACTGAGCAGTCAGGAGCTGTTCAGGCTTCTCCCAAGTGAACTCACACTCTGGGTTGACCCCTATGAAGTGTCCTACAGAATTGGAGAGGATGGCTCCATCTGTGTGCTGTATGAAGCCTCACCAGCAGGAGGTAGCACTCAAAACAGCACCAACGTGCAAATGGTAGACAGCCGAATCAGCTGTAAGGAGGAACTTCTCTTGGGCAGAACGAGCCCTTCCAAAAACTACAATAT GATGACTGTATCAGGT> SEQ ID NO: 38> CARD11 L225LI ; Length: 3465 nucleotidesATGCCGGGTGGCGGGCCGGAGATGGATGATTATATGGAAACTCTCAAAGATGAAGAAGACGCCCTGTGGGAGAACGTCGAGTGCAACCGCCACATGCTCTCCCGTTACATCAACCCAGCCAAGCTGACACCTTATCTCCGGCAGTGTAAAGTGATAGACGAACAGGACGAAGACGAAGTACTCAATGCACCCATGTTACCTAGTAAAATTAACCGTGCAGGAAGGCTGCTCGATATTCTGCACACCAAAGGTCAACGAGGCTATGTGGTGTTTCTCGAATCCTTGGAATTTTATTATCCGGAGTTGTATAAACTGGTGACAGGGAAAGAGCCAACAAGACGGTTTAGCACGATAGTGGTAGAAGAGGGGCACGAAGGTCTCACTCACTTTCTCATGAACGAAGTAATTAAGTTACAACAACAAATGAAAGCTAAAGACCTGCAAAGGTGTGAGCTCTTGGCTCGGCTCAGGCAACTGGAAGACGAAAAGAAACAAATGACACTGACACGGGTGGAACTGTTAACCTTTCAGGAGCGTTATTACAAGATGAAGGAAGAGCGGGACTCCTATAACGATGAACTGGTCAAAGTTAAGGACGATAACTACAACTTAGCAATGCGCTATGCGCAGCTCAGCGAGGAGAAGAACATGGCAGTCATGCGAAGCAGGGATCTCATTCAACTTGAAATCGATCAACTCAAGCACCGGCTCAACAAAATGGAAGAGGAATGTAAGCTCGAGCGGAATCAATCACTCAAGCTCAAGAATGACATTGAAAATCGACCAAAGAAAGAACAAGTCCTGGAACTGGAAAGGGAAAACGAAATGCTGAAGACCAAGAATCAAGAACTTCAATCCATTATTCAAGCAGGCAAGAGATCTCTGCCCGATTCCGACAAAGCAATATTGGACATTCTCGAGCACGATCGGAAGG-125-4919-8127-7289.1Atty. Dkt. No.: 121384-0284AAGCTTTAGAAGATCGACAAGAGCTGGTGAACCGCATATATAATCTTCAAGAAGAGGCCCGACAAGCAGAGGAGCTTAGGGACAAATATCTGGAAGAAAAGGAAGACTTAGAGTTGAAATGCAGCACACTTGGCAAGGACTGTGAAATGTATAAACACAGAATGAATACCGTAATGCTCCAATTGGAAGAGGTAGAAAGGGAACGGGATCAAGCTTTCCATTCACGAGACGAGGCCCAAACGCAATACTCCCAATGTCTTATCGAGAAAGATAAATATCGTAAACAAATCAGGGAGCTGGAAGAGAAGAACGATGAGATGCGTATCGAGATGGTCCGAAGAGAAGCGTGCATTGTTAACTTGGAATCAAAATTACGCCGCTTGAGTAAAGACTCCAATAATCTGGATCAATCCTTGCCCCGTAATCTGCCAGTAACCATTATTAGCCAGGATTTCGGGGATGCCAGCCCACGAACTAATGGGCAAGAAGCAGATGATTCAAGCACAAGTGAAGAGTCACCCGAAGACTCAAAGTATTTTCTGCCATACCACCCACCACAAAGAAGGATGAACCTCAAAGGGATCCAACTGCAACGCGCAAAGAGCCCCATTAGTTTGAAACGGACATCAGATTTTCAGGCTAAAGGACACGAAGAGGAAGGCACCGATGCGTCCCCATCATCCTGTGGATCCCTGCCCATAACAAACTCTTTTACAAAGATGCAACCGCCTCGATCCAGGTCTTCCATTATGAGCATCACTGCTGAACCACCAGGCAATGACTCTATTGTGAGGAGATATAAGGAAGACGCCCCACACCGCTCCACTGTAGAAGAAGATAACGATTCTGGTGGCTTCGACGCGCTGGACCTTGACGACGATTCCCACGAACGGTACAGCTTCGGCCCCTCTAGCATACACTCTTCTTCCAGTTCACATCAATCCGAAGGTCTTGATGCTTACGATCTCGAGCAAGTCAATTTGATGTTCCGTAAGTTTTCACTTGAACGACCCTTCAGACCGAGTGTTACAAGCGTTGGTCATGTTCGGGGCCCTGGTCCAAGTGTACAGCATACAACCTTGAATGGAGACTCCCTGACCAGCCAACTTACCCTCTTAGGCGGCAATGCTCGGGGCAGTTTCGTTCATTCCGTAAAACCTGGTAGCCTGGCTGAGAAAGCAGGGCTGCGCGAAGGCCACCAACTGTTGCTTTTGGAAGGTTGTATTAGAGGCGAGAGACAGTCAGTCCCACTCGATACCTGTACTAAGGAAGAAGCCCATTGGACAATCCAAAGGTGTAGCGGTCCTGTTACACTGCATTACAAAGTTAACCATGAGGGCTATAGGAAACTTGTCAAAGATATGGAAGACGGCCTTATTACATCCGGTGATTCATTTTACATACGCCTGAATCTGAACATCTCATCTCAACTCGACGCTTGCACTATGAGCCTCAAGTGTGATGACGTTGTTCACGTTCGGGACACTATGTACCAAGACCGGCACGAATGGTTATGCGCACGGGTGGATCCTTTTACTGATCATGATTTAGACATGGGTACCATTCCGAGTTACAGCAGAGCACAACAACTGCTGTTAGTCAAGCTGCAAAGGCTTATGCACCGCGGGAGTAGGGAAGAAGTAGATGGAACTCATCACACCCTCAGAGCGCTCAGAAATACACTTCAGCCCGAAGAGGCTTTGTCCACTTCAGACCCACGGGTATCACCCAGACTGTCCCGGGCGTCCTTTCTGTTTGGACAACTTCTCCAATTTGTGTCTCGTAGTGAGAACAAATACAAACGCATGAATTCTAATGAGCGGGTTCGAATTATTAGCGGCTCTCCTCTGGGATCTTTAGCACGGTCTTCTCTCGATGCTACGAAGCTGCTCACCGAAAAGCAAGAGGAACTCGATCCTGAAAGTGAGCTCGGGAAGAATCTCTCATTAATACCTTATAGTCTCGTGCGTGCCTTTTATTGTGAACGCAGGCGCCCTGTCCTTTTCACTCCAACTGTGCTGGCGAAAACGTTAGTTCAACGATTACTTAACAGCGGCGGAGCGATGGAATTCACAATTTGTAAAAGTGACATTGTTACACGCGATGAGTTTCTGAGACGCCAAAAGACCGAGACAATTATATACAGTAGAGAGAAGAATCCGAACGCTTTTGAATGCATCGCCCCCGCCAACATTGAGGCAGTCGCAGCTAAGAATAAACACTGTTTACTTGAAGCTGGCATAGGGTGTACCAGGGATCTGATTAAAAGCAATATATATCCGATAGTCCTCTTTATCCGGGTCTGCGAGAAGAATATCAAACGCTTTCGTAAATTACTCCCACGACCAGAGACCGAAGAGGAATTCCTTCGTGTTTGTAGGTTAAAAGAGAAAGAGCTCGAAGCGCTCCCATGCCTGTATGCCACTGTTGAACCTGACATGTGGGGAAGCGTGGAAGAACTGCTTAGAGTGGTGAAGGATAAAATAGGGGAAG AGCAAAGGAAGACAATTTGGGTGGACGAAGACCAACTG-126-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> SEQ ID NO: 39> CARD11 G123S ; Length: 3462 nucleotidesATGCCAGGAGGAGGGCCAGAGATGGATGACTACATGGAGACGCTGAAGGATGAAGAGGACGCCTTGTGGGAGAATGTGGAGTGTAACCGGCACATGCTCAGCCGCTATATCAACCCTGCCAAGCTCACGCCCTACCTGCGTCAGTGTAAGGTCATTGATGAGCAGGATGAAGATGAAGTGCTTAATGCCCCTATGCTGCCATCCAAGATCAACCGAGCAGGCCGGCTGTTGGACATTCTACATACCAAGGGGCAAAGGGGCTATGTGGTCTTCTTGGAGAGCCTAGAATTTTATTACCCAGAACTGTACAAACTGGTGACTGGGAAAGAGCCCACTCGGAGATTCTCCACCATTGTGGTGGAGGAAAGCCACGAGGGCCTCACGCACTTCCTGATGAACGAGGTCATCAAGCTGCAGCAGCAGATGAAGGCCAAGGACCTGCAACGCTGCGAGCTGCTGGCCAGGTTGCGGCAGCTGGAGGATGAGAAGAAGCAGATGACGCTGACGCGCGTGGAGCTGCTAACCTTCCAGGAGCGGTACTACAAGATGAAGGAAGAGCGGGACAGCTACAATGACGAGCTGGTCAAGGTGAAGGACGACAACTACAACTTAGCCATGCGCTACGCACAGCTCAGTGAGGAGAAGAACATGGCGGTCATGAGGAGCCGAGACCTCCAACTCGAGATCGATCAGCTAAAGCACCGGTTGAATAAGATGGAGGAGGAATGTAAGCTGGAGAGAAATCAGTCTCTAAAACTGAAGAATGACATTGAAAATCGGCCCAAGAAGGAGCAGGTTCTGGAACTGGAGCGGGAGAATGAAATGCTGAAGACCAAAAACCAGGAGCTGCAGTCCATCATCCAGGCCGGGAAGCGCAGCCTGCCAGACTCAGACAAGGCCATCCTGGACATCTTGGAACACGACCGCAAGGAGGCCCTGGAGGACAGGCAGGAGCTGGTCAACAGGATCTACAACCTGCAGGAGGAGGCCCGCCAGGCAGAGGAGCTGCGAGACAAGTACCTGGAGGAGAAGGAGGACCTGGAGCTCAAGTGCTCGACCCTGGGAAAGGACTGTGAAATGTACAAGCACCGCATGAACACGGTCATGCTGCAGCTGGAGGAGGTGGAGCGGGAGCGGGACCAGGCCTTCCACTCCCGAGATGAAGCTCAGACACAGTACTCGCAGTGCTTAATCGAAAAGGACAAGTACAGGAAGCAGATCCGCGAGCTGGAGGAGAAGAACGACGAGATGAGGATCGAGATGGTGCGGCGGGAGGCCTGCATCGTCAACCTGGAGAGCAAGCTGCGGCGCCTCTCCAAGGACAGCAACAACCTGGACCAGAGTCTGCCCAGGAACCTGCCAGTAACCATCATCTCTCAGGACTTTGGGGATGCCAGCCCCAGGACCAATGGTCAAGAAGCTGACGATTCTTCCACCTCGGAGGAGTCACCTGAAGACAGCAAGTACTTCCTGCCCTACCATCCGCCCCAGCGCAGGATGAACCTGAAGGGCATCCAGCTGCAGAGAGCCAAATCCCCCATCAGCCTGAAGCGAACATCAGATTTTCAAGCCAAGGGGCACGAGGAAGAAGGCACGGACGCCAGCCCTAGCTCCTGCGGATCTCTGCCCATCACCAACTCCTTCACCAAGATGCAGCCCCCCCGGAGCCGCAGCAGCATCATGTCAATCACCGCCGAGCCCCCGGGAAACGACTCCATCGTCAGACGCTACAAGGAGGACGCGCCCCATCGCAGCACAGTCGAAGAAGACAATGACAGCGGCGGGTTTGACGCCTTAGATCTGGATGATGACAGTCACGAACGCTACTCCTTCGGACCCTCCTCCATCCACTCCTCCTCCTCCTCCCACCAATCCGAGGGCCTGGATGCCTACGACCTGGAGCAGGTCAACCTCATGTTCAGGAAGTTCTCTCTGGAAAGACCCTTCCGGCCTTCGGTCACCTCTGTGGGGCACGTGCGGGGCCCAGGGCCCTCGGTGCAGCACACGACGCTGAATGGCGACAGCCTCACCTCCCAGCTCACCCTGCTGGGGGGCAACGCGCGAGGGAGCTTCGTGCACTCGGTCAAGCCTGGCTCTCTGGCCGAGAAAGCCGGCCTCCGTGAGGGCCACCAGCTGCTGCTGCTAGAAGGCTGCATCCGAGGCGAGAGGCAGAGTGTCCCGTTGGACACATGCACCAAAGAGGAAGCCCACTGGACCATCCAGAGGTGCAGCGGCCCC-127-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GTCACGCTGCACTACAAGGTCAACCACGAAGGGTACCGGAAGCTGGTGAAGGAC ATGGAGGACGGCCTGATCACATCGGGGGACTCGTTCTACATCCGGCTGAACCTGA ACATCTCCAGCCAGCTGGACGCCTGCACCATGTCCCTGAAGTGTGACGATGTTGT GCACGTCCGTGACACCATGTACCAGGACAGGCACGAGTGGCTGTGCGCGCGGGTCGACCCTTTCACAGACCATGACCTGGATATGGGCACCATACCCAGCTACAGCCGAGCCCAGCAGCTCCTCCTGGTGAAACTGCAGCGCCTGATGCACCGAGGCAGCCGG GAGGAGGTAGACGGCACCCACCACACCCTGCGGGCACTCCGGAACACCCTGCAG CCAGAAGAAGCGCTTTCAACAAGCGACCCCCGGGTCAGCCCCCGTCTCTCGCGA GCAAGCTTCCTTTTTGGCCAGCTCCTTCAGTTCGTCAGCAGGTCCGAGAACAAGTATAAGCGGATGAACAGCAACGAGCGGGTCCGCATCATCTCGGGGAGTCCGCTAGGGAGCCTGGCCCGGTCCTCGCTGGACGCCACCAAGCTCTTGACTGAGAAGCAGGA AGAGCTGGACCCTGAGAGCGAGCTGGGCAAGAACCTCAGCCTCATCCCCTACAG CCTGGTACGCGCCTTCTACTGCGAGCGCCGCCGGCCCGTGCTCTTCACACCCACC GTGCTGGCCAAGACGCTGGTGCAGAGGCTGCTCAACTCGGGAGGTGCCATGGAGTTCACCATCTGCAAGTCAGATATCGTCACAAGAGATGAGTTCCTCAGAAGGCAGA AGACGGAGACCATCATCTACTCCCGAGAGAAGAACCCCAACGCGTTCGAATGCAT CGCCCCTGCCAACATTGAAGCTGTGGCCGCCAAGAACAAGCACTGCCTGCTGGA GGCTGGGATCGGCTGCACAAGAGACTTGATCAAGTCCAACATCTACCCCATCGTGCTCTTCATCCGGGTGTGTGAGAAGAACATCAAGAGGTTCAGAAAGCTGCTGCCCC GACCTGAGACGGAGGAGGAGTTCCTGCGCGTGTGCCGGCTGAAGGAGAAGGAGC TGGAGGCCCTGCCGTGCCTGTACGCCACGGTGGAACCTGACATGTGGGGCAGCGT AGAGGAGCTGCTCCGCGTTGTCAAGGACAAGATCGGCGAGGAGCAGCGCAAGACCATCTGGGTGGACGAGGACCAGCTG>SEQ ID NO: 40> CXCR4 WT ; Length: 1071 nucleotidesATGTCCATTCCTTTGCCTCTTTTGCAGATATACACTTCAGATAACTACACCGAGGAAATGGGCTCAGGGGACTATGACTCCATGAAGGAACCCTGTTTCCGTGAAGAAAATGCTAATTTCAATAAAATCTTCCTGCCCACCATCTACTCCATCATCTTCTTAACTGGCATTGTGGGCAATGGATTGGTCATCCTGGTCATGGGTTACCAGAAGAAACTGAGAAGCATGACGGACAAGTACAGGCTGCACCTGTCAGTGGCCGACCTCCTCTTTGTCATCACGCTTCCCTTCTGGGCAGTTGATGCCGTGGCAAACTGGTACTTTGGGAACTTCCTATGCAAGGCAGTCCATGTCATCTACACAGTCAACCTCTACAGCAGTGTCCTCATCCTGGCCTTCATCAGTCTGGACCGCTACCTGGCCATCGTCCACGCCACCAACAGTCAGAGGCCAAGGAAGCTGTTGGCTGAAAAGGTGGTCTATGTTGGCGTCTGGATCCCTGCCCTCCTGCTGACTATTCCCGACTTCATCTTTGCCAACGTCAGTGAGGCAGATGACAGATATATCTGTGACCGCTTCTACCCCAATGACTTGTGGGTGGTTGTGTTCCAGTTTCAGCACATCATGGTTGGCCTTATCCTGCCTGGTATTGTCATCCTGTCCTGCTATTGCATTATCATCTCCAAGCTGTCACACTCCAAGGGCCACCAGAAGCGCAAGGCCCTCAAGACCACAGTCATCCTCATCCTGGCTTTCTTCGCCTGTTGGCTGCCTTACTACATTGGGATCAGCATCGACTCCTTCATCCTCCTGGAAATCATCAAGCAAGGGTGTGAGTTTGAGAACACTGTGCACAAGTGGATTTCCATCACCGAGGCCCTAGCTTTCTTCCACTGTTGTCTGAACCCCATCCTCTATGCTTTCCTTGGAGCCAAATTTAAAACCTCTGCCC-128-4919-8127-7289.1Atty. Dkt. No.: 121384-0284AGCACGCACTCACCTCTGTGAGCAGAGGGTCCAGCCTCAAGATCCTCTCCAAAGGAAAGCGAGGTGGACATTCATCTGTTTCCACTGAGTCTGAGTCTTCAAGTTTTCACT CCAGCTAA>SEQ ID NO: 41> DIS3 D488N ; Length: 2388 nucleotidesATGTCAGCAGACAACCAGCTGCAAGTTATCTTCATAACAAATGACAGGAGAAACAAAGAGAAAGCCATAGAAGAAGGAATACCAGCTTTCACTTGTGAAGAATATGTAAAGAGCCTAACTGCTAACCCCGAACTCATAGATCGTCTTGCTTGTTTGTCTGAAGAAGGGAATGAAATAGAAAGTGGAAAAATAATATTTTCAGAGCATCTTCCCTTAAGTAAGCTACAGCAAGGCATAAAATCTGGTACATACCTTCAAGGAACATTTAGAGCTAGCAGGGAAAATTACTTGGAAGCTACAGTATGGATTCATGGCGACAATGAAGAAAATAAAGAGATAATCTTACAGGGACTTAAACATTTAAACAGAGCTGTTCACGAAGATATTGTGGCTGTGGAGCTTCTCCCCAAGAGTCAGTGGGTAGCACCATCTTCTGTGGTTTTACATGATGAAGGTCAAAATGAAGAAGATGTGGAGAAAGAAGAAGAGACAGAACGAATGCTTAAGACTGCTGTAAGCGAGAAAATGTTGAAGCCTACAGGTAGAGTTGTAGGAATAATAAAAAGGAATTGGAGACCATATTGTGGCATGCTTTCCAAGTCTGACATTAAGGAGTCAAGAAGACATCTCTTTACACCTGCTGATAAGAGAATCCCTCGAATTCGCATAGAAACCAGACAGGCTTCCACATTAGAAGGACGGAGAATTATTGTTGCTATTGATGGTTGGCCCAGAAATTCCAGATATCCAAATGGACACTTTGTGAGAAATTTAGGTGATGTTGGAGAGAAAGAGACTGAAACAGAAGTTTTGTTACTTGAACACGATGTTCCCCATCAGCCTTTTTCACAGGCTGTTCTTAGTTTTCTGCCAAAGATGCCCTGGAGCATTACTGAAAAGGACATGAAAAACCGAGAAGACCTGAGGCATCTGTGTATTTGTAGTGTAGACCCACCAGGATGTACTGATATAGACGATGCTCTACATTGTCGAGAACTCGAAAATGGAAATTTGGAGGTTGGTGTTCATATTGCTGATGTGAGCCATTTTATTAGGCCAGGAAATGCCTTGGATCAAGAATCAGCCAGAAGAGGAACAACTGTGTATCTTTGTGAAAAGAGGATTGACATGGTTCCAGAGTTGCTTAGCTCTAACTTGTGTTCCTTAAAATGTGACGTGGACAGGCTGGCATTTTCATGTATTTGGGAAATGAATCACAATGCTGAAATCTTAAAAACGAAGTTTACCAAAAGTGTTATTAATTCAAAGGCATCTCTGACGTATGCTGAAGCTCAGTTGAGAATTGATTCAGCAAACATGAATGATGATATTACCACTAGTCTCCGTGGACTGAATAAACTAGCCAAAATTCTGAAGAAAAGAAGGATTGAAAAAGGGGCTTTGACTCTATCCTCTCCTGAAGTTCGATTCCACATGGACAGTGAAACTCACGATCCTATAAATCTGCAGACCAAGGAACTTAGGGAAACAAATTCCATGGTTGAAGAATTTATGTTACTTGCCAATATTTCTGTTGCAAAAAAAATTCATGAGGAATTTTCTGAACATGCTCTGCTTCGAAAACATCCTGCTCCACCTCCATCAAATTATGAAATTCTTGTTAAGGCAGCCAGGTCAAGGAATTTGGAAATTAAGACTGATACAGCCAAGTCTTTGGCTGAGTCTTTGGATCAGGCCGAATCTCCTACTTTTCCATATCTAAACACTCTGTTGAGAATATTAGCCACTCGCTGTATGATGCAAGCTGTGTACTTCTGTTCTGGAATGGATAATGATTTTCATCACTATGGCTTAGCGTCTCCAATATACACACATTTTACTTCACCCATTAGAAGATACGCAGATGTCATTGTTCATCGGCTTTTGGCTGTGGCTATTGGGGCTGACTGTACTTATCCAGAGTTGACAGACAAACACAAGCTTGCAGATATATGTAAAAATCTAAATTTCCGGCACAAAATGGCTCAATATGCCCAACGTGCATCAGTGGCTTTTCATACCCAGTTATTCTTCAAAAGCAAAGGAATAGTAAGTGAAGAAGCC-129-4919-8127-7289.1Atty. Dkt. No.: 121384-0284TATATTTTATTTGTAAGAAAGAATGCCATTGTGGTATTAATTCCAAAGTATGGTTTAGAAGGGACAGTCTTTTTTGAAGAAAAGGACAAACCAAACCCACAGCTTATTTATGATGATGAGATACCCTCACTTAAAATAGAAGATACAGTGTTCCATGTATTTGATAAAGTTAAAGTGAAAATCATGTTAGACTCATCTAATCTTCAACATCAGAAGATCCGAATGTCCCTGGTAGAACCACAGATACCAGGAATAAGCATTCCTACTGATACTTCAAACATGGACCTTAATGGACCAAAGAAAAAGAAGATGAAGCTTGGAAAA>SEQ ID NO: 42> ETNK1 N244S ; Length: 1356 nucleotidesATGCTCTGCGGCCGCCCGCGGTCCAGCTCCGACAACAGGAATTTTCTCCGAGAGCGGGCCGGGCTCAGTTCAGCTGCTGTCCAGACCCGGATCGGCAACAGTGCCGCCTCCAGACGTTCTCCTGCCGCTCGCCCGCCCGTCCCAGCGCCCCCAGCCCTCCCGCGAGGGCGCCCCGGGACGGAAGGATCCACCAGTCTGTCGGCGCCCGCCGTTCTCGTGGTCGCCGTCGCCGTCGTCGTGGTGGTAGTCTCCGCCGTCGCCTGGGCCATGGCCAATTACATCCACGTCCCTCCCGGCTCCCCGGAGGTGCCCAAGCTGAACGTCACCGTTCAGGATCAGGAGGAGCATCGCTGCCGGGAGGGGGCCCTGAGCCTCCTGCAACACCTGCGGCCTCACTGGGACCCCCAGGAGGTGACCCTGCAGCTCTTCACAGATGGAATCACAAATAAACTTATTGGCTGTTACGTGGGAAACACCATGGAGGATGTAGTCCTGGTGAGAATTTATGGCAATAAGACTGAGTTATTAGTCGATCGAGATGAGGAAGTAAAGAGTTTTCGAGTGTTGCAGGCTCATGGGTGTGCACCACAACTCTACTGTACCTTCAATAATGGACTATGCTATGAATTTATACAAGGAGAAGCACTGGATCCAAAGCATGTCTGCAACCCAGCCATTTTCAGGCTAATAGCTCGTCAGCTTGCTAAAATCCATGCTATTCATGCACACAGTGGCTGGATCCCCAAATCTAATCTTTGGCTAAAGATGGGAAAGTATTTCTCTCTCATTCCCACAGGATTTGCAGATGAAGACATTAATAAAAGGTTCCTAAGTGATATCCCAAGCTCTCAGATTCTCCAGGAAGAGATGACTTGGATGAAGGAGATTCTTTCCAACCTGGGCTCACCTGTTGTGCTTTGCCATAATGACCTATTGTGTAAGAATATAATCTACAATGAGAAACAAGGTGATGTACAGTTCATTGATTATGAATATTCTGGATACAACTACCTGGCATATGATATTGGAAATCATTTCAATGAATTTGCAGGTGTGAGTGATGTAGACTATAGTCTGTATCCAGATAGAGAACTACAGAGTCAGTGGCTGCGTGCTTACCTTGAAGCCTACAAAGAATTTAAGGGCTTTGGGACTGAAGTTACTGAAAAGGAGGTAGAAATACTCTTCATTCAAGTCAATCAGTTTGCATTGGCTTCTCATTTCTTTTGGGGATTGTGGGCTTTGATTCAAGCCAAATACTCCACTATTGAGTTTGATTTCCTTGGGTATGCAATTGTTCGTTTTAACCAGTACTTTAAAATGAAGCCTGAGGTTACTGCAT TAAAAGTGCCTGAG>SEQ ID NO: 43> ETS1 L23F ; Length: 675 nucleotidesATGAAGGCGGCCGTCGATCTCAAGCCGACTCTCACCATCATCAAGACGGAAAAAGTCGATCTGGAGTTTTTCCCCTCCCCGGGTAAACTCGGGGGCCAGGACTCTTTTGAAAGCATAGAGAGCTACGATAGTTGTGATCGCCTCACCCAGTCCTGGAGCAGCCAGT-130-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CATCTTTCAACAGCCTGCAGCGTGTTCCCTCCTATGACAGCTTCGACTCAGAGGACTATCCGGCTGCCCTGCCCAACCACAAGCCCAAGGGCACCTTCAAGGACTATGTGCGGGACCGTGCTGACCTCAATAAGGACAAGCCTGTCATTCCTGCTGCTGCCCTAGCTGGCTACACAGGCAGTGGACCAATCCAGCTATGGCAGTTTCTTCTGGAATTACTCACTGATAAATCCTGTCAGTCTTTTATCAGCTGGACAGGAGATGGCTGGGAATTCAAACTTTCTGACCCAGATGAGGTGGCCAGGAGATGGGGAAAGAGGAAAAACAAACCTAAGATGAATTATGAGAAACTGAGCCGTGGCCTACGCTACTATTACGACAAAAACATCATCCACAAGACAGCGGGGAAACGCTACGTGTACCGCTTTGTGTGTGACCTGCAGAGCCTGCTGGGGTACACCCCTGAGGAGCTGCACGCCATGCTGGACGTCAAGCCAGATGCCGACGAG>SEQ ID NO: 44> EZH2 W113C ; Length: 2253 nucleotidesATGGGCCAGACTGGGAAGAAATCTGAGAAGGGACCAGTTTGTTGGCGGAAGCGTGTAAAATCAGAGTACATGCGACTGAGACAGCTCAAGAGGTTCAGACGAGCTGATGAAGTAAAGAGTATGTTTAGTTCCAATCGTCAGAAAATTTTGGAAAGAACGGAAATCTTAAACCAAGAATGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACTTCTGTGAGCTCATTGCGCGGGACTAGGGAGTGTTCGGTGACCAGTGACTTGGATTTTCCAACACAAGTCATCCCATTAAAGACTCTGAATGCAGTTGCTTCAGTACCCATAATGTATTCTTGCTCTCCCCTACAGCAGAATTTTATGGTGGAAGATGAAACTGTTTTACATAACATTCCTTATATGGGAGATGAAGTTTTAGATCAGGATGGTACTTTCATTGAAGAACTAATAAAAAATTATGATGGGAAAGTACACGGGGATAGAGAATGTGGGTTTATAAATGATGAAATTTTTGTGGAGTTGGTGAATGCCCTTGGTCAATATAATGATGATGACGATGATGATGATGGAGACGATCCTGAAGAAAGAGAAGAAAAGCAGAAAGATCTGGAGGATCACCGAGATGATAAAGAAAGCCGCCCACCTCGGAAATTTCCTTCTGATAAAATTTTTGAAGCCATTTCCTCAATGTTTCCAGATAAGGGCACAGCAGAAGAACTAAAGGAAAAATATAAAGAACTCACCGAACAGCAGCTCCCAGGCGCACTTCCTCCTGAATGTACCCCCAACATAGATGGACCAAATGCTAAATCTGTTCAGAGAGAGCAAAGCTTACACTCCTTTCATACGCTTTTCTGTAGGCGATGTTTTAAATATGACTGCTTCCTACATCGTAAGTGCAATTATTCTTTTCATGCAACACCCAACACTTATAAGCGGAAGAACACAGAAACAGCTCTAGACAACAAACCTTGTGGACCACAGTGTTACCAGCATTTGGAGGGAGCAAAGGAGTTTGCTGCTGCTCTCACCGCTGAGCGGATAAAGACCCCACCAAAACGTCCAGGAGGCCGCAGAAGAGGACGGCTTCCCAATAACAGTAGCAGGCCCAGCACCCCCACCATTAATGTGCTGGAATCAAAGGATACAGACAGTGATAGGGAAGCAGGGACTGAAACGGGGGGAGAGAACAATGATAAAGAAGAAGAAGAGAAGAAAGATGAAACTTCGAGCTCCTCTGAAGCAAATTCTCGGTGTCAAACACCAATAAAGATGAAGCCAAATATTGAACCTCCTGAGAATGTGGAGTGGAGTGGTGCTGAAGCCTCAATGTTTAGAGTCCTCATTGGCACTTACTATGACAATTTCTGTGCCATTGCTAGGTTAATTGGGACCAAAACATGTAGACAGGTGTATGAGTTTAGAGTCAAAGAATCTAGCATCATAGCTCCAGCTCCCGCTGAGGATGTGGATACTCCTCCAAGGAAAAAGAAGAGGAAACACCGGTTGTGGGCTGCACACTGCAGAAAGATACAGCTGAAAAAGGACGGCTCCTCTAACCATGTTTACAACTATCAACCCTGTGATCATCCACGGCAGCCTTGTGACAGTTCGTGCCCTTGTGTGATAGCACAAAATTTTTGTGAAAAGTTTTGTCAAT-131-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GTAGTTCAGAGTGTCAAAACCGCTTTCCGGGATGCCGCTGCAAAGCACAGTGCAACACCAAGCAGTGCCCGTGCTACCTGGCTGTCCGAGAGTGTGACCCTGACCTCTGTCTTACTTGTGGAGCCGCTGACCATTGGGACAGTAAAAATGTGTCCTGCAAGAACTGCAGTATTCAGCGGGGCTCCAAAAAGCATCTATTGCTGGCACCATCTGACGTGGCAGGCTGGGGGATTTTTATCAAAGATCCTGTGCAGAAAAATGAATTCATCTCAGAATACTGTGGAGAGATTATTTCTCAAGATGAAGCTGACAGAAGAGGGAAAGTGTATGATAAATACATGTGCAGCTTTCTGTTCAACTTGAACAATGATTTTGTGGTGGATGCAACCCGCAAGGGTAACAAAATTCGTTTTGCAAATCATTCGGTAAATCCAAACTGCTATGCAAAAGTTATGATGGTTAACGGTGATCACAGGATAGGTATTTTTGCCAAGAGAGCCATCCAGACTGGCGAAGAGCTGTTTTTTGATTACAGATACAGCCAGGCTGATGCCCTGAAGTATGTCGGCATCGAAAGAGAAATGGAAATCCCT>SEQ ID NO: 45> EZH2 Y646F ; Length: 2253 nucleotidesATGGGCCAGACTGGGAAGAAATCTGAGAAGGGACCAGTTTGTTGGCGGAAGCGTGTAAAATCAGAGTACATGCGACTGAGACAGCTCAAGAGGTTCAGACGAGCTGATGAAGTAAAGAGTATGTTTAGTTCCAATCGTCAGAAAATTTTGGAAAGAACGGAAATCTTAAACCAAGAATGGAAACAGCGAAGGATACAGCCTGTGCACATCCTGACTTCTGTGAGCTCATTGCGCGGGACTAGGGAGTGTTCGGTGACCAGTGACTTGGATTTTCCAACACAAGTCATCCCATTAAAGACTCTGAATGCAGTTGCTTCAGTACCCATAATGTATTCTTGGTCTCCCCTACAGCAGAATTTTATGGTGGAAGATGAAACTGTTTTACATAACATTCCTTATATGGGAGATGAAGTTTTAGATCAGGATGGTACTTTCATTGAAGAACTAATAAAAAATTATGATGGGAAAGTACACGGGGATAGAGAATGTGGGTTTATAAATGATGAAATTTTTGTGGAGTTGGTGAATGCCCTTGGTCAATATAATGATGATGACGATGATGATGATGGAGACGATCCTGAAGAAAGAGAAGAAAAGCAGAAAGATCTGGAGGATCACCGAGATGATAAAGAAAGCCGCCCACCTCGGAAATTTCCTTCTGATAAAATTTTTGAAGCCATTTCCTCAATGTTTCCAGATAAGGGCACAGCAGAAGAACTAAAGGAAAAATATAAAGAACTCACCGAACAGCAGCTCCCAGGCGCACTTCCTCCTGAATGTACCCCCAACATAGATGGACCAAATGCTAAATCTGTTCAGAGAGAGCAAAGCTTACACTCCTTTCATACGCTTTTCTGTAGGCGATGTTTTAAATATGACTGCTTCCTACATCGTAAGTGCAATTATTCTTTTCATGCAACACCCAACACTTATAAGCGGAAGAACACAGAAACAGCTCTAGACAACAAACCTTGTGGACCACAGTGTTACCAGCATTTGGAGGGAGCAAAGGAGTTTGCTGCTGCTCTCACCGCTGAGCGGATAAAGACCCCACCAAAACGTCCAGGAGGCCGCAGAAGAGGACGGCTTCCCAATAACAGTAGCAGGCCCAGCACCCCCACCATTAATGTGCTGGAATCAAAGGATACAGACAGTGATAGGGAAGCAGGGACTGAAACGGGGGGAGAGAACAATGATAAAGAAGAAGAAGAGAAGAAAGATGAAACTTCGAGCTCCTCTGAAGCAAATTCTCGGTGTCAAACACCAATAAAGATGAAGCCAAATATTGAACCTCCTGAGAATGTGGAGTGGAGTGGTGCTGAAGCCTCAATGTTTAGAGTCCTCATTGGCACTTACTATGACAATTTCTGTGCCATTGCTAGGTTAATTGGGACCAAAACATGTAGACAGGTGTATGAGTTTAGAGTCAAAGAATCTAGCATCATAGCTCCAGCTCCCGCTGAGGATGTGGATACTCCTCCAAGGAAAAAGAAGAGGAAACACCGGTTGTGGGCTGCACACTGCAGAAAGATACAGCTGAAAAAGGACGGCTCCTCTAACCATGTTTACAACTATCAACCCTGTGATCATCCACGGCAGCCTTG-132-4919-8127-7289.1Atty. Dkt. No.: 121384-0284TGACAGTTCGTGCCCTTGTGTGATAGCACAAAATTTTTGTGAAAAGTTTTGTCAATGTAGTTCAGAGTGTCAAAACCGCTTTCCGGGATGCCGCTGCAAAGCACAGTGCAACACCAAGCAGTGCCCGTGCTACCTGGCTGTCCGAGAGTGTGACCCTGACCTCTGTCTTACTTGTGGAGCCGCTGACCATTGGGACAGTAAAAATGTGTCCTGCAAGAACTGCAGTATTCAGCGGGGCTCCAAAAAGCATCTATTGCTGGCACCATCTGACGTGGCAGGCTGGGGGATTTTTATCAAAGATCCTGTGCAGAAAAATGAATTCATCTCAGAATTCTGTGGAGAGATTATTTCTCAAGATGAAGCTGACAGAAGAGGGAAAGTGTATGATAAATACATGTGCAGCTTTCTGTTCAACTTGAACAATGATTTTGTGGTGGATGCAACCCGCAAGGGTAACAAAATTCGTTTTGCAAATCATTCGGTAAATCCAAACTGCTATGCAAAAGTTATGATGGTTAACGGTGATCACAGGATAGGTATTTTTGCCAAGAGAGCCATCCAGACTGGCGAAGAGCTGTTTTTTGATTACAGATACAGCCAGGCTGATGCCCTGAAGTATGTCGGCATCGAAAGAGAAATGGAAATCCCT>SEQ ID NO: 46> HIST1H1D A186T ; Length: 663 nucleotidesATGTCGGAGACTGCTCCACTTGCTCCTACCATTCCTGCACCCGCAGAAAAAACACCTGTGAAGAAAAAGGCGAAGAAGGCAGGCGCAACTGCTGGGAAACGCAAAGCATCCGGACCCCCAGTATCTGAGCTTATCACCAAGGCAGTGGCAGCTTCTAAGGAGCGCAGCGGCGTTTCTCTGGCCGCGCTTAAGAAAGCGCTTGCGGCTGCTGGCTACGATGTAGAAAAAAACAACAGCCGTATCAAGCTTGGCCTCAAGAGCTTGGTGAGCAAAGGTACTCTGGTGCAGACCAAAGGTACCGGTGCTTCTGGCTCCTTCAAACTCAACAAGAAAGCGGCTTCCGGGGAAGGCAAACCCAAGGCCAAAAAGGCTGGCGCAGCCAAGCCTAGGAAGCCTGCTGGGGCAGCCAAGAAGCCCAAGAAGGTGGCTGGCGCCGCTACCCCGAAGAAAAGCATCAAAAAGACTCCTAAGAAGGTAAAGAAGCCAGCAACCGCTGCTGGGACCAAGAAAGTGGCCAAGAGTGCGAAAAAGGTGAAAACACCTCAGCCAAAAAAAACTGCCAAGAGTCCAGCTAAGGCCAAAGCCCCTAAGCCCAAGGCGGCCAAGCCTAAGTCGGGGAAGCCGAAGGTTACAAAGGCAAAGAAGGCAGCTCCGAAGAAAAAG>SEQ ID NO: 47> IKZF3 L162R ; Length: 1293 nucleotidesATGGAAGATATACAAACAAATGCGGAACTGAAAAGCACTCAGGAGCAGTCTGTGCCCGCAGAAAGTGCAGCGGTTTTGAATGACTACAGTTTAACCAAATCTCATGAAATGGAAAATGTGGACAGTGGAGAAGGCCCAGCCAATGAAGATGAAGACATAGGAGATGATTCAATGAAAGTGAAAGATGAATACAGTGAAAGAGATGAGAATGTTTTAAAGTCAGAACCCATGGGAAATGCAGAAGAGCCTGAAATCCCTTACAGCTATTCAAGAGAATATAATGAATATGAAAACATTAAGTTGGAGAGACATGTTGTCTCATTCGATAGTAGCAGGCCAACCAGTGGAAAGATGAACTGCGATGTGTGTGGATTATCCTGCATCAGCTTCAATGTCTTAATGGTTCATAAGCGAAGCCATACTGGTGAACGCCCATTCCAGTGTAATCAGTGTGGGGCATCTTTTACTCAGAAAGGTAACCTCCGCCGCCACATTAAA-133-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CTGCACACAGGGGAAAAACCTTTTAAGTGTCACCTCTGCAACTATGCATGCCAAAGAAGAGATGCGCTCACGGGGCATCTTAGGACACATTCTGGTGAGAAGCGCCACTGCTTTGATGTCAACTATAATTCAAGTTACATGTATGAGAAAGAGAGTGAGCTCATACAGACCCGCATGATGGACCAAGCCATCAATAACGCCATCAGCTATCTTGGCGCCGAAGCCCTGCGCCCCTTGGTCCAGACACCGCCTGCTCCCACCTCGGAGATGGTTCCAGTTATCAGCAGCATGTATCCCATAGCCCTCACCCGGGCTGAGATGTCAAACGGTGCCCCTCAAGAGCTGGAAAAGAAAAGCATCCACCTTCCAGAGAAGAGCGTGCCTTCTGAGAGAGGCCTCTCTCCCAACAATAGTGGCCACGACTCCACGGACACTGACAGCAACCATGAAGAACGCCAGAATCACATCTATCAGCAAAATCACATGGTCCTGTCTCGGGCCCGCAATGGGATGCCACTTCTGAAGGAGGTTCCCCGCTCTTACGAACTCCTCAAGCCCCCGCCCATCTGCCCAAGAGACTCCGTCAAAGTGATCAACAAGGAAGGGGAGGTGATGGATGTGTATCGGTGTGACCACTGCCGCGTCCTCTTCCTGGACTATGTGATGTTCACGATTCACATGGGCTGCCACGGCTTCCGTGACCCTTTCGAGTGTAACATGTGTGGATATCGAAGCCATGATCGGTATGAGTTCTCGTCTCACATAGCCAGAGGAGAACACAGAGCCCTGCTGAAG>SEQ ID NO: 48> IRF4 E66K ; Length: 1353 nucleotidesATGAACCTGGAGGGCGGCGGCCGAGGCGGAGAGTTCGGCATGAGCGCGGTGAGCTGCGGCAACGGGAAGCTCCGCCAGTGGCTGATCGACCAGATCGACAGCGGCAAGTACCCCGGGCTGGTGTGGGAGAACGAGGAGAAGAGCATCTTCCGCATCCCCTGGAAGCACGCGGGCAAGCAGGACTACAACCGCGAGAAGGACGCCGCGCTCTTCAAGGCTTGGGCACTGTTTAAAGGAAAGTTCCGAGAAGGCATCGACAAGCCGGACCCTCCCACCTGGAAGACGCGCCTGCGGTGCGCTTTGAACAAGAGCAATGACTTTGAGGAACTGGTTGAGCGGAGCCAGCTGGACATCTCAGACCCGTACAAAGTGTACAGGATTGTTCCTGAGGGAGCCAAAAAAGGAGCCAAGCAGCTCACCCTGGAGGACCCGCAGATGTCCATGAGCCACCCCTACACCATGACAACGCCTTACCCTTCGCTCCCAGCCCAGCAGGTTCACAACTACATGATGCCACCCCTCGACCGAAGCTGGAGGGACTACGTCCCGGATCAGCCACACCCGGAAATCCCGTACCAATGTCCCATGACGTTTGGACCCCGCGGCCACCACTGGCAAGGCCCAGCTTGTGAAAATGGTTGCCAGGTGACAGGAACCTTTTATGCTTGTGCCCCACCTGAGTCCCAGGCTCCCGGAGTCCCCACAGAGCCAAGCATAAGGTCTGCCGAAGCCTTGGCGTTCTCAGACTGCCGGCTGCACATCTGCCTGTACTACCGGGAAATCCTCGTGAAGGAGCTGACCACGTCCAGCCCCGAGGGCTGCCGGATCTCCCATGGACATACGTATGACGCCAGCAACCTGGACCAGGTCCTGTTCCCCTACCCAGAGGACAATGGCCAGAGGAAAAACATTGAGAAGCTGCTGAGCCACCTGGAGAGGGGCGTGGTCCTCTGGATGGCCCCCGACGGGCTCTATGCGAAAAGACTGTGCCAGAGCAGGATCTACTGGGACGGGCCCCTGGCGCTGTGCAACGACCGGCCCAACAAACTGGAGAGAGACCAGACCTGCAAGCTCTTTGACACACAGCAGTTCTTGTCAGAGCTGCAAGCGTTTGCTCACCACGGCCGCTCCCTGCCAAGATTCCAGGTGACTCTATGCTTTGGAGAGGAGTTTCCAGACCCTCAGAGGCAAAGAAAGCTCATCACAGCTCACGTAGAACCTCTGCTAGCCAGACAACTATATTATTTTGCTCAACAAAACAGTGGACATTTCCTGAGGGGCTACGATTTACCAGAACACATCAGCAATCCAGAAGATTACCACAGATCTATCCGCCATTCCTCTATTCAAGAA-134-4919-8127-7289.1Atty. Dkt. No.: 121384-0284>SEQ ID NO: 49> KLHL6 L90V ; Length: 1863 nucleotidesATGTTGATGGCAGGACAAAGGGGCGCCTGGACCATGGGTGATGTGGTCGAGAAGAGTTTGGAAGGGCCCCTGGCACCTTCTACAGATGAGCCCTCCCAGAAAACAGGAGACTTGGTCGAGATCTTAAATGGGGAAAAGGTCAAATTTGACGACGCGGGACTCTCCTTAATTCTTCAGAATGGCCTGGAAACCCTGCGAATGGAAAACGCTCTGACAGATGTCATCTTGTGTGTGGACATTCAGGAATTCTCCTGCCACCGCGTGGTGGTTGCCGCAGCCAGCAACTATTTCAGGGCCATGTTCTGCAACGATTTAAAGGAAAAGTATGAGAAAAGGATCATTATTAAAGGGGTTGATGCTGAGACCATGCACACTCTGTTGGACTACACGTACACCAGCAAGGCGCTGATCACCAAGCAGAATGTCCAGCGGGTCCTGGAGGCTGCTAACCTCTTCCAGTTCCTGCGGATGGTGGATGCCTGTGCCAGCTTCCTCACTGAAGCCTTGAACCCAGAAAACTGCGTTGGAATACTGAGGCTGGCTGACACACACTCGCTGGACAGTCTAAAGAAGCAGGTTCAGAGTTACATCATTCAAAACTTTGTGCAGATTCTGAACTCTGAGGAGTTTCTTGACCTGCCCGTGGACACTCTGCACCACATCTTGAAGAGTGATGACCTTTACGTGACCGAGGAGGCTCAGGTGTTTGAGACCGTGATGAGCTGGGTCCGGCACAAGCCATCAGAACGACTCTGCTTACTCCCCTATGTCCTCGAGAACGTGCGCTTACCGCTTCTGGACCCGTGGTACTTTGTGGAGACGGTGGAAGCAGATCCTCTCATCAGGCAGTGCCCAGAGGTCTTCCCGCTGCTCCAGGAAGCCAGGATGTACCACCTTTCTGGCAATGAGATCATTTCGGAACGCACCAAGCCCAGGATGCATGAGTTCCAGTCTGAGGTGTTCATGATCATTGGCGGCTGCACGAAGGATGAACGGTTTGTGGCAGAGGTGACCTGCCTGGACCCCCTGAGGCGCAGCCGCCTGGAGGTGGCCAAGCTCCCGCTAACAGAGCATGAGCTGGAGAGTGAGAATAAGAAGTGGGTGGAGTTTGCATGCGTGACATTGAAAAATGAGGTCTACATCTCAGGTGGCAAAGAAACACAGCATGATGTTTGGAAATATAATTCTTCGATCAACAAGTGGATTCAGATTGAGTATTTAAACATAGGCCGCTGGAGGCATAAGATGGTGGTGTTGGGTGGCAAGGTCTATGTGATCGGAGGCTTTGACGGCTTACAGAGAATCAACAATGTGGAGACCTACGACCCCTTTCACAACTGCTGGTCAGAGGCCGCACCCCTCCTTGTCCATGTCAGTTCCTTTGCAGCCACCAGCCATAAGAAGAAGCTGTATGTGATCGGGGGAGGGCCCAATGGGAAACTGGCCACAGACAAGACTCAGTGTTATGACCCTTCCACCAACAAGTGGAGTTTGAAGGCGGCCATGCCCGTGGAGGCTAAATGCATCAATGCAGTGAGTTTCCGGGACCGCATCTATGTCGTTGGTGGGGCCATGAGAGCGCTGTACGCCTACAGCCCGCTGGAAGACAGCTGGTGCCTGGTGACCCAGCTCAGCCACGAGCGGGCCAGCTGCGGTATCGCGCCCTGCAACAACCGGCTCTACATCACCGGCGGGCGGGACGAGAAGAACGAGGTTATCGCCACGGTGCTGTGCTGGGACCCCGAGGCCCAGAAACTGACAGAGGAGTGCGTCCTGCCCCGGGGCGTGTCGCACCACGGCAGCGTCACCATCAGGAAGTCGTACACCCACATCCGCAGGATCGTGCCCGGAGCAGTGTCTGTC>SEQ ID NO: 50> MAP2K2 Q60P ; Length: 1200 nucleotides-135-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ATGCTGGCCCGGAGGAAGCCGGTGCTGCCGGCGCTCACCATCAACCCTACCATCGCCGAGGGCCCATCCCCTACCAGCGAGGGCGCCTCCGAGGCAAACCTGGTGGACCTGCAGAAGAAGCTGGAGGAGCTGGAACTTGACGAGCAGCAGAAGAAGCGGCTGGAAGCCTTTCTCACCCCGAAAGCCAAGGTCGGCGAACTCAAAGACGATGACTTCGAAAGGATCTCAGAGCTGGGCGCGGGCAACGGCGGGGTGGTCACCAAAGTCCAGCACAGACCCTCGGGCCTCATCATGGCCAGGAAGCTGATCCACCTTGAGATCAAGCCGGCCATCCGGAACCAGATCATCCGCGAGCTGCAGGTCCTGCACGAATGCAACTCGCCGTACATCGTGGGCTTCTACGGGGCCTTCTACAGTGACGGGGAGATCAGCATTTGCATGGAACACATGGACGGCGGCTCCCTGGACCAGGTGCTGAAAGAGGCCAAGAGGATTCCCGAGGAGATCCTGGGGAAAGTCAGCATCGCGGTTCTCCGGGGCTTGGCGTACCTCCGAGAGAAGCACCAGATCATGCACCGAGATGTGAAGCCCTCCAACATCCTCGTGAACTCTAGAGGGGAGATCAAGCTGTGTGACTTCGGGGTGAGCGGCCAGCTCATCGACTCCATGGCCAACTCCTTCGTGGGCACGCGCTCCTACATGGCTCCGGAGCGGTTGCAGGGCACACATTACTCGGTGCAGTCGGACATCTGGAGCATGGGCCTGTCCCTGGTGGAGCTGGCCGTCGGAAGGTACCCCATCCCCCCGCCCGACGCCAAAGAGCTGGAGGCCATCTTTGGCCGGCCCGTGGTCGACGGGGAAGAAGGAGAGCCTCACAGCATCTCGCCTCGGCCGAGGCCCCCCGGGCGCCCCGTCAGCGGTCACGGGATGGATAGCCGGCCTGCCATGGCCATCTTTGAACTCCTGGACTATATTGTGAACGAGCCACCTCCTAAGCTGCCCAACGGTGTGTTCACCCCCGACTTCCAGGAGTTTGTCAATAAATGCCTCATCAAGAACCCAGCGGAGCGGGCGGACCTGAAGATGCTCACAAACCACACCTTCATCAAGCGGTCCGAGGTGGAAGAAGTGGATTTTGCCGGCTGGTTGTGTAAAACCCTGCGGCTGAACCAGCCCGGCACACCCACGCGCACCGCCGTG>SEQ ID NO: 51> mCXCR4 S345* ; Length: 1023 nucleotidesATGGAACCAATCTCCGTCTCCATATATACCAGTGATAATTACAGCGAAGAAGTGGGTAGCGGTGACTACGACTCAAATAAAGAGCCTTGCTTCAGGGACGAAAATGTCCATTTTAACCGGATCTTCTTGCCCACTATCTATTTTATAATTTTCCTGACCGGAATAGTAGGCAACGGGCTCGTGATTCTGGTTATGGGTTATCAAAAGAAGTTGAGATCTATGACCGATAAGTATCGCTTGCACCTAAGTGTCGCGGATCTCCTGTTTGTCATCACCCTTCCATTTTGGGCGGTTGATGCGATGGCAGATTGGTACTTTGGAAAATTCCTCTGCAAGGCAGTACACATAATATACACCGTTAATCTTTACTCCTCAGTCCTCATCCTGGCATTTATCTCCCTAGATCGGTACTTGGCTATCGTCCACGCAACTAATAGCCAGAGACCCAGAAAACTTCTGGCAGAGAAGGCCGTGTACGTTGGCGTGTGGATACCGGCCTTGCTCCTGACTATACCCGATTTCATTTTCGCCGATGTTTCCCAAGGGGACATCAGCCAAGGAGATGACCGCTATATCTGTGATAGGCTGTATCCTGATTCCCTCTGGATGGTGGTCTTCCAATTTCAACACATCATGGTAGGGCTCATTCTACCAGGAATAGTTATTCTGTCCTGCTATTGCATAATCATATCAAAACTCTCACATAGTAAAGGCCACCAGAAACGTAAAGCCCTGAAGACCACGGTAATCCTGATCCTTGCATTCTTTGCATGCTGGCTGCCGTACTATGTTGGCATATCCATTGACTCTTTCATCCTGCTCGGAGTAATCAAGCAAGGGTGCGATTTTGAATCAATTGTGCATAAGTGGATCTCAATAACCGAGGCGTTGGCCTTCTTTCATTGCTGCCTCAACCCAATACTGTATGCCTTTCTCGGAGCCAAGTTCAAGAGCTCCGCA-136-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CAACATGCCCTGAATTCTATGTCCAGAGGAAGCAGCCTCAAAATCCTTTCCAAAGGCAAAAGG>SEQ ID NO: 52> mIL4R L243N ; Length: 2430 nucleotidesATGGGCCGTCTATGTACAAAATTCCTTACAAGTGTAGGGTGTCTCATCCTTCTGCTTGTGACAGGAAGCGGTTCTATAAAGGTTCTGGGCGAGCCCACATGCTTTTCCGATTACATCAGAACGAGCACTTGTGAGTGGTTCCTAGACTCCGCAGTCGACTGTTCCTCTCAACTTTGTCTCCATTATCGCCTCATGTTCTTTGAGTTTTCCGAGAACCTCACCTGCATACCTCGCAATAGTGCCAGTACTGTGTGTGTATGCCACATGGAAATGAACCGACCCGTTCAATCCGACCGATATCAGATGGAGCTTTGGGCCGAACATAGGCAATTGTGGCAAGGGAGCTTTTCCCCATCTGGGAACGTAAAGCCTCTCGCGCCGGATAACCTAACGCTACATACTAACGTGAGCGATGAGTGGTTGCTTACATGGAACAACCTCTATCCTAGTAACAATCTCCTGTATAAGGATCTCATATCAATGGTGAACATTAGTCGAGAGGATAATCCAGCTGAATTTATCGTATACAACGTCACCTACAAGGAGCCACGTCTTTCTTTTCCTATTAATATCCTAATGTCCGGCGTCTACTATACTGCACGCGTGAGAGTTCGCAGCCAAATTCTTACTGGCACTTGGAGTGAATGGAGCCCGTCTATTACTTGGTATAATCATT TCCAACTACCCCTTATTCAACGCCTACCTTTGGGCGTCACTATCAGTTGTAACTGCA TTCCGCTATTTTGCCTCTTTTGTTACTTCTCAATAACTAAAATAAAGAAAATTTGGT GGGATCAAATACCAACGCCCGCACGCAGCCCTCTCGTCGCGATTATTATTCAAGATGCACAGGTGCCACTGTGGGACAAGCAAACCCGATCACAGGAGAGCACGAAGTATCCACATTGGAAAACGTGTCTAGATAAGCTTTTGCCCTGTCTTCTTAAACACAGGGTTAAGAAGAAGACTGATTTCCCCAAGGCTGCCCCTACGAAATCCCTGCAATCTCCCGGTAAGGCAGGCTGGTGCCCAATGGAAGTTAGCCGCACAGTACTTTGGCCTGAAAATGTTTCTGTGTCCGTGGTCAGATGCATGGAGCTTTTCGAAGCGCCTGTCCAAAACGTGGAAGAGGAAGAAGATGAAATCGTGAAAGAAGATCTGAGCATGAGTCCGGAGAACTCAGGCGGGTGTGGTTTCCAGGAGTCCCAAGCCGACATTATGGCTCGGCTCACCGAAAACCTGTTTAGCGATCTCCTCGAGGCTGAAAACGGTGGCCTCGGCCAAAGCGCACTTGCTGAGTCATGTTCTCCTCTCCCTTCAGGGAGCGGCCAAGCTAGCGTCAGCTGGGCCTGCTTGCCTATGGGTCCTAGCGAGGAAGCCACATGCCAAGTGACTGAGCAACCTAGTCATCCAGGGCCTCTTAGCGGAAGCCCTGCCCAATCCGCACCTACTCTGGCCTGTACGCAGGTCCCATTGGTGTTGGCCGATAATCCGGCTTACCGCAGCTTCTCCGACTGTTGTAGCCCCGCTCCCAATCCAGGCGAACTGGCCCCAGAGCAGCAACAAGCTGATCACTTGGAAGAGGAAGAGCCACCTAGCCCAGCTGACCCCCACTCTTCTGGTCCCCCTATGCAACCCGTTGAATCTTGGGAACAAATTTTGCATATGTCAGTTCTTCAACACGGAGCAGCTGCAGGGTCTACCCCTGCTCCAGCTGGTGGGTACCAAGAGTTCGTGCAAGCAGTTAAGCAAGGAGCCGCCCAAGATCCAGGGGTCCCGGGCGTGCGGCCTTCCGGAGATCCTGGTTACAAGGCATTTTCATCACTCCTCTCTTCTAATGGGATCCGAGGCGACACTGCTGCCGCTGGGACAGATGACGGTCATGGCGGATATAAGCCATTCCAAAACCCTGTGCCGAACCAATCTCCCTCTTCTGTACCTCTGTTTACATTTGGTCTGGATACAGAACTGTCCCCTAGTCCCTTGAATAGCGATCCGCCCAAAAGCCCACCGGAATGTCTCGGCCTCGAACTCGGACTGAAAGGTGGTGACTGGGTAAAAG CCCCACCACCAGCTGACCAGGTGCCCAAACCCTTTGGTGACGATTTGGGCTTCGG-137-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GATAGTATACAGCTCCCTCACCTGCCACCTGTGCGGGCATCTCAAACAACATCACAGCCAAGAGGAAGGCGGACAATCACCCATAGTCGCTTCACCCGGATGCGGCTGTTGTTATGACGATCGTTCACCTTCCCTAGGCTCCCTTAGCGGTGCTCTCGAGTCATGTCCTGAGGGCATACCACCAGAAGCAAACTTGATGTCCGCTCCCAAAACACCTTCAAACCTAAGCGGCGAAGGTAAAGGCCCCGGGCATAGCCCCGTGCCTTCACAAACGACCGAGGTACCAGTGGGCGCACTTGGAATCGCGGTTTCC>SEQ ID NO: 53> mPDCDl WT ; Length: 864 nucleotidesATGTGGGTCCGACAAGTACCATGGTCTTTCACTTGGGCAGTACTCCAACTTTCCTGGCAGTCCGGATGGCTACTGGAAGTACCTAATGGACCCTGGCGCTCTTTGACATTTTATCCGGCGTGGCTCACGGTAAGCGAGGGCGCCAACGCAACCTTTACTTGCTCATTGTCTAATTGGTCTGAGGACCTGATGCTAAACTGGAATCGCCTTAGTCCGTCTAACCAGACCGAAAAGCAAGCGGCGTTTTGTAATGGCTTGAGCCAACCCGTTCAAGACGCTCGATTTCAAATTATCCAACTCCCTAACCGCCATGATTTTCATATGAATATCCTAGATACACGGCGCAACGACTCTGGCATCTACCTTTGCGGAGCAATCAGCTTGCATCCAAAAGCCAAAATTGAGGAATCACCAGGGGCAGAACTTGTTGTCACCGAAAGAATCCTTGAAACATCAACTAGGTATCCATCACCTTCACCCAAACCTGAAGGACGCTTTCAGGGAATGGTGATTGGAATTATGTCAGCCCTTGTAGGAATTCCTGTACTGCTGCTGCTTGCATGGGCTTTGGCGGTCTTTTGTAGCACATCCATGTCCGAGGCAAGGGGAGCCGGTAGTAAGGACGACACTCTGAAAGAGGAACCATCTGCCGCACCAGTTCCAAGTGTTGCGTATGAGGAACTTGACTTCCAAGGGCGCGAGAAAACACCCGAACTGCCAACTGCCTGCGTCCATACGGAGTATGCTACTATAGTATTTACGGAAGGATTGGGCGCATCTGCAATGGGGCGTCGAGGTTCAGCAGATGGTCTCCAAGGGCCTCGGCCACCCCGGCATGAGGACGGTCACTGTAGCTGGCCACTC>SEQ ID NO: 54> MYD88 WT ; Length: 927 nucleotidesATGCGACCCGACCGCGCTGAGGCTCCAGGACCGCCCGCCATGGCTGCAGGAGGTCCCGGCGCGGGGTCTGCGGCCCCGGTCTCCTCCACATCCTCCCTTCCCCTGGCTGCTCTCAACATGCGAGTGCGGCGCCGCCTGTCTCTGTTCTTGAACGTGCGGACACAGGTGGCGGCCGACTGGACCGCGCTGGCGGAGGAGATGGACTTTGAGTACTTGGAGATCCGGCAACTGGAGACACAAGCGGACCCCACTGGCAGGCTGCTGGACGCCTGGCAGGGACGCCCTGGCGCCTCTGTAGGCCGACTGCTCGAGCTGCTTACCAAGCTGGGCCGCGACGACGTGCTGCTGGAGCTGGGACCCAGCATTGAGGAGGATTGCCAAAAGTATATCTTGAAGCAGCAGCAGGAGGAGGCTGAGAAGCCTTTACAGGTGGCCGCTGTAGACAGCAGTGTCCCACGGACAGCAGAGCTGGCGGGCATCACCACACTTGATGACCCCCTGGGGCATATGCCTGAGCGTTTCGATGCCTTCATCTGCTATTGCCCCAGCGACATCCAGTTTGTGCAGGAGATGATCCGGCAACTGGAACAGACAAACTATCGACTGAAGTTGTGTGTGTCTGACCGCGATGTCCTGCCTGGCACCTGTGTCTGGTCTAT-138-4919-8127-7289.1Atty. Dkt. No.: 121384-0284TGCTAGTGAGCTCATCGAAAAGAGGTGCCGCCGGATGGTGGTGGTTGTCTCTGATGATTACCTGCAGAGCAAGGAATGTGACTTCCAGACCAAATTTGCACTCAGCCTCTCTCCAGGTGCCCATCAGAAGCGACTGATCCCCATCAAGTACAAGGCAATGAAGAAAGAGTTCCCCAGCATCCTGAGGTTCATCACTGTCTGCGACTACACCAACCCCTGCACCAAATCTTGGTTCTGGACTCGCCTTGCCAAGGCCTTGTCCCTGCCC>SEQ ID NO: 55> NKAP V405D ; Length: 1245 nucleotidesATGGCTCCGGTGTCCGGCTCACGCAGCCCGGATAGGGAGGCCTCGGGCTCGGGGGGAAGACGTCGCAGTTCGTCGAAGAGTCCGAAGCCCAGCAAATCTGCCCGCTCCCCGCGGGGCCGCCGCTCTCGCTCGCACTCTTGCTCTCGGTCCGGGGACCGGAATGGACTCACCCATCAGCTGGGTGGCCTCAGCCAAGGCTCCCGAAACCAGTCCTACCGCTCACGCTCGCGGTCGCGTTCTAGAGAGCGGCCCTCTGCGCCCCGGGGCATCCCCTTCGCTTCTGCCTCCTCGTCAGTCTATTACGGCAGCTACTCGCGCCCCTACGGGAGCGACAAGCCTTGGCCTAGCCTCCTCGACAAGGAGAGGGAGGAGAGCCTGCGGCAGAAGAGATTAAGTGAGAGAGAGAGAATTGGAGAATTGGGAGCTCCTGAAGTATGGGGACTTTCTCCAAAGAATCCTGAACCAGATTCTGATGAACATACACCAGTGGAGGATGAAGAGCCAAAGAAAAGCACTACTTCAGCTTCTACTTCAGAAGAAGAAAAAAAGAAGAAGTCTAGCCGTTCAAAAGAAAGGTCCAAGAAAAGGAGAAAGAAAAAATCATCGAAAAGAAAACATAAGAAGTATTCTGAAGATAGCGACAGTGACTCTGATTCTGAAACAGACTCCAGTGATGAAGATAACAAAAGGAGAGCAAAGAAAGCCAAGAAAAAGGAAAAGAAGAAGAAACACAGATCGAAGAAATATAAGAAAAAGAGGTCTAAGAAGAGCAGAAAAGAGTCCAGTGATTCAAGCTCTAAAGAATCCCAAGAAGAGTTTCTGGAAAATCCCTGGAAGGATCGAACAAAGGCTGAAGAACCATCAGATTTAATTGGCCCAGAGGCTCCAAAAACACTTACCTCTCAAGATGATAAACCTTTGAACTATGGCCATGCTCTGTTACCTGGTGAAGGTGCAGCTATGGCTGAATATGTAAAAGCTGGAAAACGTATCCCACGAAGAGGTGAAATTGGCTTGACAAGTGAAGAAATTGCATCATTTGAATGCTCAGGTTATGTAATGAGTGGTAGCAGGCATCGCCGAATGGAGGCTGTGCGACTGCGAAAAGAGAACCAGATCTACAGTGCTGATGAGAAGAGAGCCCTTGCATCCTTTAACCAAGAAGAGAGACGAAAGAGAGAGAACAAGATTCTGGCCAGTTT TCGAGAAATGGATTACAGAAAGACCAAAGGGAAGGATGACAAA>SEQ ID NO: 56> PIM1 P81S ; Length: 939 nucleotidesATGCTCTTGTCCAAAATCAACTCGCTTGCCCACCTGCGCGCCGCGCCCTGCAACGACCTGCACGCCACCAAGCTGGCGCCCGGCAAGGAGAAGGAGCCCCTGGAGTCGCAGTACCAGGTGGGCCCGCTACTGGGCAGCGGCGGCTTCGGCTCGGTCTACTCAGGCATCCGCGTCTCCGACAACTTGCCGGTGGCCATCAAACACGTGGAGAAGGACCGGATTTCCGACTGGGGAGAGCTGTCTAATGGCACTCGAGTGCCCATGGAAGTGGTCCTGCTGAAGAAGGTGAGCTCGGGTTTCTCCGGCGTCATTAGGCTCCTGGACTGGTT-139-4919-8127-7289.1Atty. Dkt. No.: 121384-0284CGAGAGGCCCGACAGTTTCGTCCTGATCCTGGAGAGGCCCGAGCCGGTGCAAGATCTCTTCGACTTCATCACGGAAAGGGGAGCCCTGCAAGAGGAGCTGGCCCGCAGCTTCTTCTGGCAGGTGCTGGAGGCCGTGCGGCACTGCCACAACTGCGGGGTGCTCCACCGCGACATCAAGGACGAAAACATCCTTATCGACCTCAATCGCGGCGAGCTCAAGCTCATCGACTTCGGGTCGGGGGCGCTGCTCAAGGACACCGTCTACACGGACTTCGATGGGACCCGAGTGTATAGCCCTCCAGAGTGGATCCGCTACCATCGCTACCATGGCAGGTCGGCGGCAGTCTGGTCCCTGGGGATCCTGCTGTATGATATGGTGTGTGGAGATATTCCTTTCGAGCATGACGAAGAGATCATCAGGGGCCAGGTTTTCTTCAGGCAGAGGGTCTCTTCAGAATGTCAGCATCTCATTAGATGGTGCTTGGCCCTGAGACCATCAGATAGGCCAACCTTCGAAGAAATCCAGAACCATCCATGGATGCAAGATGTTCTCCTGCCCCAGGAAACTGCTGAGATCCACCTCCACAGCCTGTCGCCGGGGCCCAGCA AA>SEQ ID NO: 57> PIM2 E31D ; Length: 933 nucleotidesATGTTGACCAAGCCTCTACAGGGGCCTCCCGCGCCCCCCGGGACCCCCACGCCGCCGCCAGGAGGCAAGGATCGGGAAGCGTTCGAGGCCGACTATCGACTCGGCCCCCTCCTGGGTAAGGGGGGCTTTGGCACCGTCTTCGCAGGACACCGCCTCACAGATCGACTCCAGGTGGCCATCAAAGTGATTCCCCGGAATCGTGTGCTGGGCTGGTCCCCCTTGTCAGACTCAGTCACATGCCCACTCGAAGTCGCACTGCTATGGAAAGTGGGTG CAGGTGGTGGGCACCCTGGCGTGATCCGCCTGCTTGACTGGTTTGAGACACAGGA GGGCTTCATGCTGGTCCTCGAGCGGCCTTTGCCCGCCCAGGATCTCTTTGACTATA TCACAGAGAAGGGCCCACTGGGTGAAGGCCCAAGCCGCTGCTTCTTTGGCCAAGTAGTGGCAGCCATCCAGCACTGCCATTCCCGTGGAGTTGTCCATCGTGACATCAAGGATGAGAACATCCTGATAGACCTACGCCGTGGCTGTGCCAAACTCATTGATTTTGGTTCTGGTGCCCTGCTTCATGATGAACCCTACACTGACTTTGATGGGACAAGGGTGTACAGCCCCCCAGAGTGGATCTCTCGACACCAGTACCATGCACTCCCGGCCACTGTCTGGTCACTGGGCATCCTCCTCTATGACATGGTGTGTGGGGACATTCCCTTTGAGAGGGACCAGGAGATTCTGGAAGCTGAGCTCCACTTCCCAGCCCATGTCTCCCCAGA CTGCTGTGCCCTAATCCGCCGGTGCCTGGCCCCCAAACCTTCTTCCCGACCCTCAC TGGAAGAGATCCTGCTGGACCCCTGGATGCAAACACCAGCCGAGGATGTACCCCT CAACCCCTCCAAAGGAGGCCCTGCCCCTTTGGCCTGGTCCTTGCTACCC>SEQ ID NO: 58> PPP4C D54N ; Length: 921 nucleotidesATGGCGGAGATCAGCGACCTGGACCGGCAGATCGAGCAGCTGCGTCGCTGCGAGCTCATCAAGGAGAGCGAAGTCAAGGCCCTGTGCGCTAAGGCCAGAGAGATCTTGGTAGAGGAGAGCAACGTGCAGAGGGTGGACTCGCCAGTCACAGTGTGCGGCAACATCCATGGACAATTCTATGACCTCAAAGAGCTGTTCAGAGTAGGTGGCGACGTCCCTGAGACCAACTACCTCTTCATGGGGGACTTTGTGGACCGTGGCTTCTATAGCGTCG-140-4919-8127-7289.1Atty. Dkt. No.: 121384-0284AAACGTTCCTCCTGCTGCTGGCACTTAAGGTTCGCTATCCTGATCGCATCACACTGATCCGGGGCAACCATGAGAGTCGCCAGATCACGCAGGTCTATGGCTTCTACGATGAGTGCCTGCGCAAGTACGGCTCGGTGACTGTGTGGCGCTACTGCACTGAGATCTTTGACTACCTCAGCCTGTCAGCCATCATCGATGGCAAGATCTTCTGCGTGCACGGGGGCCTCTCCCCCTCCATCCAGACCCTGGATCAGATTCGGACAATCGACCGAAAGCAAGAGGTGCCTCATGATGGGCCCATGTGTGACCTCCTCTGGTCTGACCCAGAAGACACCACAGGCTGGGGCGTGAGCCCCCGAGGAGCCGGCTACCTATTTGGCAGTGACGTGGTGGCCCAGTTCAACGCAGCCAATGACATTGACATGATCTGCCGTGCCCACCAACTGGTGATGGAAGGTTACAAGTGGCACTTCAATGAGACGGTGCTCACTGTGTGGTCGGCACCCAACTACTGCTACCGCTGTGGGAATGTGGCAGCCATCTTGGAGCTGGACGAGCATCTCCAGAAAGATTTCATCATCTTTGAGGCTGCTCCCCAAGAGACACGGGGCATCCCCTCCAAGAAGCCCGTGGCCGACTACTTCCTG>SEQ ID NO: 59> PTPN11 WT ; Length: 1779 nucleotidesATGACATCGCGGAGATGGTTTCACCCAAATATCACTGGTGTGGAGGCAGAAAACCTACTGTTGACAAGAGGAGTTGATGGCAGTTTTTTGGCAAGGCCTAGTAAAAGTAACCCTGGAGACTTCACACTTTCCGTTAGAAGAAATGGAGCTGTCACCCACATCAAGATTCAGAACACTGGTGATTACTATGACCTGTATGGAGGGGAGAAATTTGCCACTTTGGCTGAGTTGGTCCAGTATTACATGGAACATCACGGGCAATTAAAAGAGAAGAATGGAGATGTCATTGAGCTTAAATATCCTCTGAACTGTGCAGATCCTACCTCTGAAAGGTGGTTTCATGGACATCTCTCTGGGAAAGAAGCAGAGAAATTATTAACTGAAAAAGGAAAACATGGTAGTTTTCTTGTACGAGAGAGCCAGAGCCACCCTGGAGATTTTGTTCTTTCTGTGCGCACTGGTGATGACAAAGGGGAGAGCAATGACGGCAAGTCTAAAGTGACCCATGTTATGATTCGCTGTCAGGAACTGAAATACGACGTTGGTGGAGGAGAACGGTTTGATTCTTTGACAGATCTTGTGGAACATTATAAGAAGAATCCTATGGTGGAAACATTGGGTACAGTACTACAACTCAAGCAGCCCCTTAACACGACTCGTATAAATGCTGCTGAAATAGAAAGCAGAGTTCGAGAACTAAGCAAATTAGCTGAGACCACAGATAAAGTCAAACAAGGCTTTTGGGAAGAATTTGAGACACTACAACAACAGGAGTGCAAACTTCTCTACAGCCGAAAAGAGGGTCAAAGGCAAGAAAACAAAAACAAAAATAGATATAAAAACATCCTGCCCTTTGATCATACCAGGGTTGTCCTACACGATGGTGATCCCAATGAGCCTGTTTCAGATTACATCAATGCAAATATCATCATGCCTGAATTTGAAACCAAGTGCAACAATTCAAAGCCCAAAAAGAGTTACATTGCCACACAAGGCTGCCTGCAAAACACGGTGAATGACTTTTGGCGGATGGTGTTCCAAGAAAACTCCCGAGTGATTGTCATGACAACGAAAGAAGTGGAGAGAGGAAAGAGTAAATGTGTCAAATACTGGCCTGATGAGTATGCTCTAAAAGAATATGGCGTCATGCGTGTTAGGAACGTCAAAGAAAGCGCCGCTCATGACTATACGCTAAGAGAACTTAAACTTTCAAAGGTTGGACAAGGGAATACGGAGAGAACGGTCTGGCAATACCACTTTCGGACCTGGCCGGACCACGGCGTGCCCAGCGACCCTGGGGGCGTGCTGGACTTCCTGGAGGAGGTGCACCATAAGCAGGAGAGCATCATGGATGCAGGGCCGGTCGTGGTGCACTGCAGTGCTGGAATTGGCCGGACAGGGACGTTCATTGTGATTGATATTCTTATTGACATCATCAGAGAGAAAGGTGTTGACTGCGATATTGACGTTCCCAAAACCATCCAGATGGTGCGGTCTCAGAGGTCAGGGATGGTCCAGACAGAAGCACAGTACCGATTTATCTAT-141-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ATGGCGGTCCAGCATTATATTGAAACACTACAGCGCAGGATTGAAGAAGAGCAGAAAAGCAAGAGGAAAGGGCACGAATATACAAATATTAAGTATTCTCTAGCGGACCAGACGAGTGGAGATCAGAGCCCTCTCCCGCCTTGTACTCCAACGCCACCCTGTGCAGAAATGAGAGAAGACAGTGCTAGAGTCTATGAAAACGTGGGCCTGATGCAACAG CAGAAAAGTTTCAGA>SEQ ID NO: 60> RFTN1 S255R ; Length: 1734 nucleotidesATGGGTTGCGGATTGAACAAGTTAGAGAAACGTGATGAAAAACGGCCTGGGAATATTTATTCAACTTTGAAGAGGCCTCAGGTGGAAACCAAGATAGATGTGTCCTATGAATACCGCTTCCTGGAGTTCACGACTCTGAGTGCTGCGGAGCTCCCTGGGTCCTCAGCAGTGAGGCTGGCCTCCCTGCGTGACCTGCCCGCCCAGCTCCTGGAGCTGTACCAGCAGGGCTTCTCGCTGGCGGCCCTGCACCCCTTCGTGCAGCCCACCCATGAGCGGGAGAAGACGCCCCTGGAGCACATCTTTAGAGCCATCCTGATCAAGAAAACCGACAGATCTCAGAAAACTGATCTTCACAATGAAGGCTACATCTTGGAATTAGATTGCTGTTCCTCCTTAGACCACCCGACAGACCAGAAACTCATCCCAGAGTTCATTAAGAAGATCCAGGAGGCTGCAAGCCAGGGCCTGAAATTCGTTGGTGTTATACCTCAGTACCATTCCTCTGTGAACTCGGCAGGCAGCAGTGCTCCGGTGTCTACTGCCAACAGCACCGAGGATGCCAGAGATGCAAAAAACGCACGTGGGGATCACGCGTCACTGGAGAATGAGAAACCGGGGACTGGGGATGTGTGCAGTGCTCCGGCTGGGAGAAACCAAAGCCCAGAGCCCAGCTCAGGCCCCAGAGGGGAGGTGCCCCTCGCCAAGCAGCCCAGCTCACCCTCCGGAGAGGGAGATGGTGGAGAACTTTCACCACAGGGGGTGAGGAAGACACTGGATGGACCGGAGAGCAACCCCTTGGAGGTGCATGAAGAGCCACTCTCAGGGAAAATGGAGATCTTCACCCTTTTCAACAAACCGAAGAGCCATCAGAAGTGCCGGCAATACTACCCTGTCACCATTCCTCTCCATGTCTCCAAGAATGGCCAGACAGTGAGCGGTTTGGACGCCAACTGGTTAGAGCACATGAGCGACCACTTCCGGAAAGGAGGCATGCTGGTGAACGCAGTCTTCTACCTTGGAATAGTGAATGATTCCTTACATGGCTTGACAGATGGAGTATTCATCTTTGAAGCTGTTTCCACAGAAGATAGCAAAACCATACAGGGCTATGATGCTATTGTGGTTGAACAATGGACAGTCCTGGAAGGTGTCGAAGTGCAGACAGACTACGTGCCCCTGCTGAACTCGCTGGCGGCCTATGGCTGGCAGCTCACCTGTGTGCTACCAACTCCCGTCGTCAAGACTACCAGCGAGGGGAGTGTATCCACCAAGCAGATTGTCTTTCTTCAGAGACCTTGTCTACCTCAGAAAATCAAGAAGAAGGAATCGAAGTTTCAGTGGCGATTCTCCAGAGAAGAAATGCACAACAGGCAGATGAGGAAATCAAAAGGTAAACTCAGTGCCAGAGACAAACAACAAGCAGAAGAAAATGAGAAGAACTTAGAAGACCAGTCTTCCAAAGCTGGAGACATGGGAAACTGTGTTTCAGGACAGCAGCAGGAGGGTGGAGTCTCCGAGGAGATGAAGGGCCCTGTCCAAGAGGACAAGGGAGAACAGCTGTCCCCTGGTGGCCTGCTGTGTGGGGTGGGTGTGGAGGGTGAGGCTGTGCAGAATGGTCCTGCCAGCCACAGCAGGGCCCTGGTGGGGATTTGCACTGGGCACTCCAATCCTGGAGAGGATGCCAGGGACGGGGATGCTGAGGAAGTCAGAGAGCTTGGTACGGTTGAAGAAAAC>SEQ ID NO: 61-142-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> S0CS1 A17T ; Length: 633 nucleotidesATGGTAGCACACAACCAGGTGGCAGCCGACAATGCAGTCTCCACAGCAACAGAGCCCCGACGGCGGCCAGAACCTTCCTCCTCTTCCTCCTCCTCGCCCGCGGCCCCCG CGCGCCCGCGGCCGTGCCCCGCGGTCCCGGCCCCGGCCCCCGGCGACACGCACTT CCGCACATTCCGTTCGCACGCCGATTACCGGCGCATCACGCGCGCCAGCGCGCTC CTGGACGCCTGCGGATTCTACTGGGGGCCCCTGAGCGTGCACGGGGCGCACGAGCGGCTGCGCGCCGAGCCCGTGGGCACCTTCCTGGTGCGCGACAGCCGCCAGCGGAACTGCTTTTTCGCCCTTAGCGTGAAGATGGCCTCGGGACCCACGAGCATCCGCG TGCACTTTCAGGCCGGCCGCTTTCACCTGGATGGCAGCCGCGAGAGCTTCGACTG CCTCTTCGAGCTGCTGGAGCACTACGTGGCGGCGCCGCGCCGCATGCTGGGGGCC CCGCTGCGCCAGCGCCGCGTGCGGCCGCTGCAGGAGCTGTGCCGCCAGCGCATCGTGGCCACCGTGGGCCGCGAGAACCTGGCTCGCATCCCCCTCAACCCCGTCCTCC GCGACTACCTGAGCTCCTTCCCCTTCCAGATT>SEQ ID NO: 62> TBL1XR1 Y446S ; Length: 1542 nucleotidesATGAGTATAAGCAGTGATGAGGTCAACTTCTTGGTATATAGATACTTGCAAGAGTCAGGATTTTCTCATTCAGCATTTACCTTTGGTATAGAAAGCCATATCAGTCAGTCCAATATAAATGGTGCCCTCGTCCCACCCGCTGCATTGATTTCTATCATCCAGAAAGGTCTACAGTATGTAGAAGCAGAAGTTAGTATTAATGAGGATGGTACCTTGTTTGATGGTCGACCAATAGAGTCTCTGTCCCTGATAGATGCCGTAATGCCTGATGTAGTACAAACAAGACAACAAGCTTATAGAGATAAGCTTGCACAGCAACAGGCAGCAGCTGCTGCAGCTGCCGCAGCTGCAGCCAGCCAACAAGGATCTGCAAAAAATGGAGAAAACACAGCAAATGGGGAGGAGAATGGAGCACATACTATAGCAAATAATCATACTGATATGATGGAAGTGGATGGGGATGTTGAAATCCCTCCTAATAAAGCTGTTGTGTTGCGGGGCCATGAATCTGAAGTTTTTATCTGTGCCTGGAACCCTGTTAGTGATCTCCTAGCATCAGGGTCTGGAGACTCAACAGCAAGAATATGGAATCTTAGTGAGAACAGCACCAGTGGCTCTACACAGTTAGTACTTAGACATTGTATACGAGAAGGAGGGCAAGATGTTCCAAGCAACAAGGATGTCACATCTCTAGATTGGAATAGTGAAGGTACACTTCTAGCAACTGGTTCCTATGATGGGTTTGCCAGAATATGGACTAAAGATGGTAACCTTGCTAGCACCTTAGGGCAGCATAAAGGCCCTATATTTGCATTAAAATGGAATAAGAAAGGAAATTTCATCCTAAGTGCTGGAGTAGACAAGACTACAATTATTTGGGACGCACATACTGGTGAAGCCAAGCAACAGTTTCCTTTTCATTCAGCACCAGCATTGGATGTTGATTGGCAGAGCAACAACACCTTTGCTTCTTGTAGTACAGATATGTGCATTCATGTCTGTAAATTAGGACAAGACAGACCTATTAAAACATTCCAAGGACATACGAATGAAGTAAATGCTATCAAATGGGACCCAACTGGCAATCTCTTGGCCTCCTGTTCTGACGACATGACTTTAAAGATATGGAGTATGAAACAAGACAATTGTGTCCATGATTTGCAAGCACATAATAAAGAAATTTATACTATCAAATGGAGTCCAACAGGACCAGGGACTAATAATCCAAATGCCAACCTTATGTTAGCAAGTGCATCCTTTGATTCTACTGTTAGGTTATGGGATGTAGACCGAGGGATATGCATCCATACCTTGACAAAACACCAAGAGCCTGTGTCCAGTGTAGCTTTCAGTCCTGATGGCAGGTATCTGGCAAGTGGTTCTTTTGACAAATGTGTACACATCTGGAACACGCAGACAGGTGCTCTAGTTCACAGCTATAGGGGAACAG-143-4919-8127-7289.1Atty. Dkt. No.: 121384-0284GTGGAATATTTGAAGTTTGCTGGAATGCAGCAGGAGACAAAGTTGGAGCCAGTGCATCAGATGGTTCAGTTTGTGTATTAGACCTTCGGAAA>SEQ ID NO: 63> TBL1XR1 WT ; Length: 1545 nucleotidesATGAGTATAAGCAGTGATGAGGTCAACTTCTTGGTATATAGATACTTGCAAGAGTCAGGATTTTCTCATTCAGCATTTACCTTTGGTATAGAAAGCCATATCAGTCAGTCCAATATAAATGGTGCCCTCGTCCCACCCGCTGCATTGATTTCTATCATCCAGAAAGGTCTACAGTATGTAGAAGCAGAAGTTAGTATTAATGAGGATGGTACCTTGTTTGATGGTCGACCAATAGAGTCTCTGTCCCTGATAGATGCCGTAATGCCTGATGTAGTACAAACAAGACAACAAGCTTATAGAGATAAGCTTGCACAGCAACAGGCAGCAGCTGCTGCAGCTGCCGCAGCTGCAGCCAGCCAACAAGGATCTGCAAAAAATGGAGAAAACACAGCAAATGGGGAGGAGAATGGAGCACATACTATAGCAAATAATCATACTGATATGATGGAAGTGGATGGGGATGTTGAAATCCCTCCTAATAAAGCTGTTGTGTTGCGGGGCCATGAATCTGAAGTTTTTATCTGTGCCTGGAACCCTGTTAGTGATCTCCTAGCATCAGGGTCTGGAGACTCAACAGCAAGAATATGGAATCTTAGTGAGAACAGCACCAGTGGCTCTACACAGTTAGTACTTAGACATTGTATACGAGAAGGAGGGCAAGATGTTCCAAGCAACAAGGATGTCACATCTCTAGATTGGAATAGTGAAGGTACACTTCTAGCAACTGGTTCCTATGATGGGTTTGCCAGAATATGGACTAAAGATGGTAACCTTGCTAGCACCTTAGGGCAGCATAAAGGCCCTATATTTGCATTAAAATGGAATAAGAAAGGAAATTTCATCCTAAGTGCTGGAGTAGACAAGACTACAATTATTTGGGACGCACATACTGGTGAAGCCAAGCAACAGTTTCCTTTTCATTCAGCACCAGCATTGGATGTTGATTGGCAGAGCAACAACACCTTTGCTTCTTGTAGTACAGATATGTGCATTCATGTCTGTAAATTAGGACAAGACAGACCTATTAAAACATTCCAAGGACATACGAATGAAGTAAATGCTATCAAATGGGACCCAACTGGCAATCTCTTGGCCTCCTGTTCTGACGACATGACTTTAAAGATATGGAGTATGAAACAAGACAATTGTGTCCATGATTTGCAAGCACATAATAAAGAAATTTATACTATCAAATGGAGTCCAACAGGACCAGGGACTAATAATCCAAATGCCAACCTTATGTTAGCAAGTGCATCCTTTGATTCTACTGTTAGGTTATGGGATGTAGACCGAGGGATATGCATCCATACCTTGACAAAACACCAAGAGCCTGTGTACAGTGTAGCTTTCAGTCCTGATGGCAGGTATCTGGCAAGTGGTTCTTTTGACAAATGTGTACACATCTGGAACACGCAGACAGGTGCTCTAGTTCACAGCTATAGGGGAACAGGTGGAATATTTGAAGTTTGCTGGAATGCAGCAGGAGACAAAGTTGGAGCCAGTGCATCAGATGGTTCAGTTTGTGTATTAGACCTTCGGAAATAG>SEQ ID NO: 64> tCD19 WT ; Length: 951 nucleotidesATGCCACCTCCTCGCCTCCTCTTCTTCCTCCTCTTCCTCACCCCCATGGAAGTCAGGCCCGAGGAACCTCTAGTGGTGAAGGTGGAAGAGGGAGATAACGCTGTGCTGCAGTGCCTCAAGGGGACCTCAGATGGCCCCACTCAGCAGCTGACCTGGTCTCGGGAGTCCCCGCTTAAACCCTTCTTAAAACTCAGCCTGGGGCTGCCAGGCCTGGGAATCC-144-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ACATGAGGCCCCTGGCCATCTGGCTTTTCATCTTCAACGTCTCTCAACAGATGGGGGGCTTCTACCTGTGCCAGCCGGGGCCCCCCTCTGAGAAGGCCTGGCAGCCTGGCTGGACAGTCAATGTGGAGGGCAGCGGGGAGCTGTTCCGGTGGAATGTTTCGGACCTAGGTGGCCTGGGCTGTGGCCTGAAGAACAGGTCCTCAGAGGGCCCCAGCTCCCCTTCCGGGAAGCTCATGAGCCCCAAGCTGTATGTGTGGGCCAAAGACCGCCCTGAGATCTGGGAGGGAGAGCCTCCGTGTCTCCCACCGAGGGACAGCCTGAACCAGAGCCTCAGCCAGGACCTCACCATGGCCCCTGGCTCCACACTCTGGCTGTCCTGTGGGGTACCCCCTGACTCTGTGTCCAGGGGCCCCCTCTCCTGGACCCATGTGCACCCCAAGGGGCCTAAGTCATTGCTGAGCCTAGAGCTGAAGGACGATCGCCCGGCCAGAGATATGTGGGTAATGGAGACGGGTCTGTTGTTGCCCCGGGCCACAGCTCAAGACGCTGGAAAGTATTATTGTCACCGTGGCAACCTGACCATGTCATTCCACCTGGAGATCACTGCTCGGCCAGTACTATGGCACTGGCTGCTGAGGACTGGTGGCTGGAAGGTCTCAGCTGTGACTTTGGCTTATCTGATCTTCTGCCTGTGTTCCCTTGTGGGCATTCTTCATCTTCAAAGAGCCCTG>SEQ ID NO: 65> tCD20 WT ; Length: 870 nucleotidesATGACAACACCCAGAAATTCAGTAAATGGGACTTTCCCGGCAGAGCCAATGAAAGGCCCTATTGCTATGCAATCTGGTCCAAAACCACTCTTCAGGAGGATGTCTTCACTGGTGGGCCCCACGCAAAGCTTCTTCATGAGGGAATCTAAGACTTTGGGGGCTGTCCAGATTATGAATGGGCTCTTCCACATTGCCCTGGGGGGTCTTCTGATGATCCCAGCAGGGATCTATGCACCCATCTGTGTGACTGTGTGGTACCCTCTCTGGGGAGGCATTATGTATATTATTTCCGGATCACTCCTGGCAGCAACGGAGAAAAACTCCAGGAAGTGTTTGGTCAAAGGAAAAATGATAATGAATTCATTGAGCCTCTTTGCTGCCATTTCTGGAATGATTCTTTCAATCATGGACATACTCAACATCAAGATCAGCCACTTCCTTAAGATGGAAAGCCTGAACTTCATCAGAGCTCACACACCATATATTAACATATACAACTGTGAACCAGCTAATCCCTCTGAGAAAAACTCCCCATCTACCCAATACTGTTACAGCATACAATCTCTGTTCTTGGGCATTTTGTCAGTGATGCTGATCTTTGCCTTCTTCCAGGAACTTGTAATAGCTGGCATCGTTGAGAATGAATGGAAAAGAAACATAGTTCTCCTGTCAGCAGAAGAAAAAAAAGAACAGACTATTGAAATAAAAGAAGAAGTGGTTGGGCTAACTGAAACATCTTCCCAACCAAAGAATGAAGAAGACATTGAAATTATTCCAATCCAAGAAGAGGAAGAAGAAGAAACAGAGACGAACTTTCCAGAACCTCCCCAAGATCAGGAATCCTCACCAATAGAAAATGACAGCTCTCCT>SEQ ID NO: 66> TLR2 D327V ; Length: 2352 nucleotidesATGCCACATACTTTGTGGATGGTGTGGGTCTTGGGGGTCATCATCAGCCTCTCCAAGGAAGAATCCTCCAATCAGGCTTCTCTGTCTTGTGACCGCAATGGTATCTGCAAGGGCAGCTCAGGATCTTTAAACTCCATTCCCTCAGGGCTCACAGAAGCTGTAAAAAGCCTTGACCTGTCCAACAACAGGATCACCTACATTAGCAACAGTGACCTACAGAGG-145-4919-8127-7289.1Atty. Dkt. No.: 121384-0284TGTGTGAACCTCCAGGCTCTGGTGCTGACATCCAATGGAATTAACACAATAGAGG AAGATTCTTTTTCTTCCCTGGGCAGTCTTGAACATTTAGACTTATCCTATAATTACTT ATCTAATTTATCGTCTTCCTGGTTCAAGCCCCTTTCTTCTTTAACATTCTTAAACTTA CTGGGAAATCCTTACAAAACCCTAGGGGAAACATCTCTTTTTTCTCATCTCACAAA ATTGCAAATCCTGAGAGTGGGAAATATGGACACCTTCACTAAGATTCAAAGAAAA GATTTTGCTGGACTTACCTTCCTTGAGGAACTTGAGATTGATGCTTCAGATCTACA GAGCTATGAGCCAAAAAGTTTGAAGTCAATTCAGAATGTAAGTCATCTGATCCTTC ATATGAAGCAGCATATTTTACTGCTGGAGATTTTTGTAGATGTTACAAGTTCCGTGG AATGTTTGGAACTGCGAGATACTGATTTGGACACTTTCCATTTTTCAGAACTATCCA CTGGTGAAACAAATTCATTGATTAAAAAGTTTACATTTAGAAATGTGAAAATCACC GATGAAAGTTTGTTTCAGGTTATGAAACTTTTGAATCAGATTTCTGGATTGTTAGA ATTAGAGTTTGATGACTGTACCCTTAATGGAGTTGGTAATTTTAGAGCATCTGATAA TGACAGAGTTATAGATCCAGGTAAAGTGGAAACGTTAACAATCCGGAGGCTGCAT ATTCCAAGGTTTTACTTATTTTATGTTCTGAGCACTTTATATTCACTTACAGAAAGA GTTAAAAGAATCACAGTAGAAAACAGTAAAGTTTTTCTGGTTCCTTGTTTACTTTC ACAACATTTAAAATCATTAGAATACTTGGATCTCAGTGAAAATTTGATGGTTGAAG AATACTTGAAAAATTCAGCCTGTGAGGATGCCTGGCCCTCTCTACAAACTTTAATT TTAAGGCAAAATCATTTGGCATCATTGGAAAAAACCGGAGAGACTTTGCTCACTC TGAAAAACTTGACTAACATTGATATCAGTAAGAATAGTTTTCATTCTATGCCTGAAA CTTGTCAGTGGCCAGAAAAGATGAAATATTTGAACTTATCCAGCACACGAATACAC AGTGTAACAGGCTGCATTCCCAAGACACTGGAAATTTTAGATGTTAGCAACAACA ATCTCAATTTATTTTCTTTGAATTTGCCGCAACTCAAAGAACTTTATATTTCCAGAA ATAAGTTGATGACTCTACCAGATGCCTCCCTCTTACCCATGTTACTAGTATTGAAAA TCAGTAGGAATGCAATAACTACGTTTTCTAAGGAGCAACTTGACTCATTTCACACA CTGAAGACTTTGGAAGCTGGTGGCAATAACTTCATTTGCTCCTGTGAATTCCTCTC CTTCACTCAGGAGCAGCAAGCACTGGCCAAAGTCTTGATTGATTGGCCAGCAAAT TACCTGTGTGACTCTCCATCCCATGTGCGTGGCCAGCAGGTTCAGGATGTCCGCCT CTCGGTGTCGGAATGTCACAGGACAGCACTGGTGTCTGGCATGTGCTGTGCTCTG TTCCTGCTGATCCTGCTCACGGGGGTCCTGTGCCACCGTTTCCATGGCCTGTGGTATATGAAAATGATGTGGGCCTGGCTCCAGGCCAAAAGGAAGCCCAGGAAAGCTCC CAGCAGGAACATCTGCTATGATGCATTTGTTTCTTACAGTGAGCGGGATGCCTACT GGGTGGAGAACCTTATGGTCCAGGAGCTGGAGAACTTCAATCCCCCCTTCAAGTT GTGTCTTCATAAGCGGGACTTCATTCCTGGCAAGTGGATCATTGACAATATCATTGA CTCCATTGAAAAGAGCCACAAAACTGTCTTTGTGCTTTCTGAAAACTTTGTGAAG AGTGAGTGGTGCAAGTATGAACTGGACTTCTCCCATTTCCGTCTTTTTGATGAGAA CAATGATGCTGCCATTCTCATTCTTCTGGAGCCCATTGAGAAAAAAGCCATTCCCC AGCGCTTCTGCAAGCTGCGGAAGATAATGAACACCAAGACCTACCTGGAGTGGCC CATGGACGAGGCTCAGCGGGAAGGATTTTGGGTAAATCTGAGAGCTGCGATAAAG TCC>SEQ ID NO: 67> USP8 K657E ; Length: 3354 nucleotides-146-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ATGCCTGCTGTGGCTTCAGTTCCTAAAGAACTCTACCTCAGTTCTTCACTAAAAGA CCTTAATAAGAAGACAGAAGTTAAACCAGAGAAAATAAGCACTAAGAGTTATGTG CACAGTGCCCTGAAGATCTTTAAGACAGCAGAAGAATGCAGATTAGATCGTGATG AGGAAAGGGCCTATGTACTATATATGAAATACGTGACTGTTTATAATCTTATCAAAA AAAGACCTGATTTCAAGCAACAGCAGGATTATTTCCATTCAATACTTGGACCTGGA AACATCAAAAAAGCTGTCGAAGAAGCTGAAAGACTCTCTGAAAGCCTTAAATTAA GATATGAAGAAGCTGAAGTCCGGAAAAAACTTGAGGAAAAAGACAGGCAGGAG GAAGCACAGCGGCTACAACAAAAAAGGCAGGAAACAGGAAGAGAGGATGGTGG CACATTGGCTAAAGGCTCTTTGGAGAATGTTTTGGATTCCAAAGACAAAACCCAA AAGAGCAATGGTGAAAAGAATGAAAAATGTGAGACCAAAGAGAAAGGAGCAATC ACAGCAAAGGAACTATACACAATGATGACGGATAAAAACATCAGCTTGATTATAAT GGATGCTCGAAGAATGCAGGATTATCAGGATTCCTGTATTTTACATTCTCTCAGTGT TCCTGAAGAAGCCATCAGTCCAGGAGTCACTGCTAGTTGGATTGAAGCACACCTG CCAGATGATTCTAAAGACACATGGAAGAAGAGGGGGAATGTGGAGTATGTGGTAC TTCTTGACTGGTTTAGTTCTGCCAAAGATTTACAGATTGGAACAACTCTCCGGAGT CTGAAAGATGCACTTTTCAAGTGGGAAAGTAAAACTGTCCTGCGCAATGAGCCTT TGGTTTTAGAGGGAGGCTATGAAAACTGGCTCCTTTGTTATCCCCAGTATACAACA AATGCTAAGGTCACTCCACCCCCACGACGCCAGAATGAAGAGGTGTCTATCTCATT GGATTTTACTTATCCCTCATTGGAAGAATCAATTCCTTCTAAACCTGCTGCCCAGAC GCCACCTGCATCTATAGAAGTAGATGAAAATATAGAATTGATAAGTGGTCAAAATG AGAGAATGGGACCACTGAATATATCAACTCCAGTTGAACCAGTTGCTGCTTCTAAA TCTGATGTTTCACCCATAATTCAGCCAGTGCCTAGTATAAAGAATGTTCCACAGATT GATCGTACTAAAAAACCAGCAGTCAAATTGCCTGAAGAGCATAGAATAAAATCTG AAAGTACAAACCATGAGCAACAATCTCCTCAGAGTGGAAAAGTTATTCCTGATCGTTCCACCAAGCCAGTAGTTTTTTCTCCAACTCTCATGTTAACAGATGAAGAAAAGG CTCGTATTCATGCAGAAACTGCTCTTCTAATGGAAAAAAACAAACAAGAAAAAGA ACTTCGGGAAAGGCAGCAAGAGGAACAGAAAGAGAAACTGAGGAAGGAAGAAC AAGAACAAAAAGCCAAAAAGAAACAAGAAGCTGAAGAAAATGAAATTACAGAG AAGCAACAAAAAGCAAAAGAAGAAATGGAGAAGAAAGAAAGTGAACAGGCCAA GAAAGAAGATAAAGAAACCTCAGCAAAGAGGGGCAAAGAAATAACAGGAGTAA AAAGACAAAGTAAAAGTGAACATGAAACTTCTGATGCCAAGAAATCTGTAGAAG ATAGGGGGAAAAGGTGTCCAACCCCAGAAATACAGAAAAAGTCAACAGGAGATG TGCCCCATACATCTGTGACAGGGGATTCAGGTTCAGGCAAGCCATTTAAGATTAAA GGACAACCAGAAAGTGGAATTCTAAGGACAGGAACTTTTAGAGAGGATACAGAC GATACCGAAAGAAATAAAGCTCAACGAGAACCTTTGACAAGAGCACGAAGTGAA GAAATGGGGAGGATCGTACCAGGACTGCCTTCAGGCTGGGCCGAGTTTCTTGACC CAATCACTGGAACCTTTCGTTATTATCATTCACCCACCAACACTGTTCATATGTACC CACCGGAAATGGCTCCTTCATCTGCACCTCCTTCCACCCCTCCAACTCATAAAGCC AAGCCACAGATTCCTGCTGAGCGGGATAGGGAACCTTCCAAACTGAAGCGCTCCT ACTCCTCCCCAGATATAACCCAGGCTATTCAAGAGGAAGAGAAGAGGAAGCCAAC AGTAACTCCAACAGTTAATCGGGAAAACAAGCCAACATGTTATCCTAAAGCTGAG ATCTCAAGGCTTTCTGCTTCTCAGATTCGGAACCTCAATCCTGTTTTTGGAGGTTCT GGACCAGCTCTTACTGGACTTCGTAACTTAGGAAATACTTGTTATATGAACTCAATA TTGCAGTGCCTATGTAACGCTCCACATTTGGCTGATTATTTCAACCGAAACTGTTAT CAGGATGATATTAACAGGTCAAATTTGTTGGGGCATAAAGGTGAAGTGGCAGAAG AATTTGGTATAATCATGAAAGCCCTGTGGACAGGACAGTATAGATATATCAGTCCA AAGGACTTTAAAATCACCATTGGGAAGATCAATGACCAGTTTGCAGGATACAGTC-147-4919-8127-7289.1Atty. Dkt. No.: 121384-0284AGCAAGATTCACAAGAATTGCTTCTGTTCCTAATGGATGGTCTCCATGAAGATCTAAATAAAGCTGATAATCGGAAGAGATATAAAGAAGAAAATAATGATCATCTCGATGACTTTAAAGCTGCAGAACATGCCTGGCAGAAACACAAGCAGCTCAATGAGTCTATTATTGTTGCACTTTTTCAGGGTCAATTCAAATCTACAGTACAGTGCCTCACATGTCACAAAAAGTCTAGGACATTTGAGGCCTTCATGTATTTGTCTCTACCACTAGCATCCACAAGTAAATGTACATTACAGGATTGCCTTAGATTATTTTCCAAAGAAGAAAAACTCACAGATAACAACAGATTTTACTGCAGTCATTGCAGAGCTCGACGGGATTCTCTAAAAAAGATAGAAATCTGGAAGTTACCACCTGTGCTTTTAGTGCATCTGAAACGTTTTTCCTACGATGGCAGGTGGAAACAAAAATTACAGACATCTGTGGACTTCCCGTTAGAAAATCTTGACTTGTCACAGTATGTTATTGGTCCAAAGAACAATTTGAAGAAATATAATTTGTTTTCTGTTTCAAATCACTACGGTGGGCTGGATGGAGGCCACTACACAGCCTATTGTAAAAATGCAGCAAGACAACGGTGGTTTAAGTTTGATGATCATGAAGTTTCTGATATCTCCGTTTCTTCTGTGAAATCTTCAGCAGCTTATATCCTCTTTTATACTTCATTGGGACCACGAGTAACTGATGTAGCCACA>SEQ ID NO: 68> XP01 WT ; Length: 3213 nucleotidesATGCCAGCAATTATGACAATGTTAGCAGACCATGCAGCTCGTCAGCTGCTTGATTTCAGCCAAAAACTGGATATCAACTTATTAGATAATGTGGTGAATTGCTTATACCATGGAGAAGGAGCCCAGCAAAGAATGGCTCAAGAAGTACTGACACATTTAAAGGAGCATCCTGATGCTTGGACAAGAGTCGACACAATTTTGGAATTTTCTCAGAATATGAATACGAAATACTATGGACTACAAATTTTGGAAAATGTGATAAAAACAAGGTGGAAGATTCTTCCAAGGAACCAGTGCGAAGGAATAAAAAAATACGTTGTTGGCCTCATTATCAAGACGTCATCTGACCCAACTTGTGTAGAGAAAGAAAAGGTGTATATCGGAAAATTAAATATGATCCTTGTTCAGATACTGAAACAAGAATGGCCCAAACATTGGCCAACTTTTATCAGTGATATTGTTGGAGCAAGTAGGACCAGCGAAAGTCTCTGTCAAAATAATATGGTGATTCTTAAACTCTTGAGTGAAGAAGTATTTGATTTCTCTAGTGGACAGATAACCCAAGTCAAATCTAAGCATTTAAAAGACAGCATGTGCAATGAATTCTCACAGATATTTCAACTGTGTCAGTTTGTAATGGAAAATTCTCAAAATGCTCCACTTGTACATGCAACCTTGGAAACATTGCTCAGATTTCTGAACTGGATTCCCCTGGGATATATTTTTGAGACCAAATTAATCAGCACATTGATTTATAAGTTCCTGAATGTTCCAATGTTTCGAAATGTCTCTCTGAAGTGCCTCACTGAGATTGCTGGTGTGAGTGTAAGCCAATATGAAGAACAATTTGTAACACTATTTACTCTGACAATGATGCAACTAAAGCAGATGCTTCCTTTAAATACCAATATTCGACTTGCGTACTCAAATGGAAAAGATGATGAACAGAACTTCATTCAAAATCTCAGTTTGTTTCTCTGCACCTTTCTTAAGGAACATGATCAACTTATAGAAAAAAGATTAAATCTCAGGGAAACTCTTATGGAGGCCCTTCATTATATGTTGTTGGTATCTGAAGTAGAAGAAACTGAAATCTTTAAAATTTGTCTTGAATACTGGAATCATTTGGCTGCTGAACTCTATAGAGAGAGTCCATTCTCTACATCTGCCTCTCCGTTGCTTTCTGGAAGTCAACATTTTGATGTTCCTCCCAGGAGACAGCTATATTTGCCCATGTTATTCAAGGTCCGTTTATTAATGGTTAGTCGAATGGCTAAACCAGAGGAAGTATTGGTTGTAGAGAATGATCAAGGAGAAGTTGTGAGAGAATTCATGAAGGATACAGATTCCATAAATTTGTATAAGAATATGAGGGAAACATTGGTTTATCTTACTCATCTGGATTATGTAGATACAGAAAGAATAATGACAGAGAAGCTTCACAATCAAGTGAATGGTAC-148-4919-8127-7289.1Atty. Dkt. No.: 121384-0284AGAGTGGTCATGGAAAAATTTGAATACATTGTGTTGGGCAATAGGCTCCATTAGTGGAGCAATGCATGAAGAGGACGAAAAACGATTTCTTGTTACTGTTATAAAGGATCTATTAGGATTATGTGAACAGAAAAGAGGCAAAGATAATAAAGCTATTATTGCATCAAATATCATGTACATAGTAGGTCAATACCCACGTTTTTTGAGAGCTCACTGGAAATTTCTGAAGACTGTAGTTAACAAGCTGTTCGAATTCATGCATGAGACCCATGATGGAGTCCAGGATATGGCTTGTGATACTTTCATTAAAATAGCCCAAAAATGCCGCAGGCATTTCGTTCAGGTTCAGGTTGGAGAAGTGATGCCATTTATTGATGAAATTTTGAACAACATTAACACTATTATTTGTGATCTTCAGCCTCAACAGGTTCATACGTTTTATGAAGCTGTGGGGTACATGATTGGTGCACAAACAGATCAAACAGTACAAGAACACTTGATAGAAAAGTACATGTTACTCCCTAATCAAGTGTGGGATAGTATAATCCAGCAGGCAACCAAAAATGTGGATATACTGAAAGATCCTGAAACAGTCAAGCAGCTTGGTAGCATTTTGAAAACAAATGTGAGAGCCTGCAAAGCTGTTGGACACCCCTTTGTAATTCAGCTTGGAAGAATTTATTTAGATATGCTTAATGTATACAAGTGCCTCAGTGAAAATATTTCTGCAGCTATCCAAGCTAATGGTGAAATGGTTACAAAGCAACCATTGATTAGAAGTATGCGAACTGTAAAAAGGGAAACTTTAAAGTTAATATCTGGTTGGGTGAGCCGATCCAATGATCCACAGATGGTCGCTGAAAATTTTGTTCCCCCTCTGTTGGATGCAGTTCTCATTGATTATCAGAGAAATGTCCCAGCTGCTAGAGAACCAGAAGTGCTTAGTACTATGGCCATAATTGTCAACAAGTTAGGGGGACATATAACAGCTGAAATACCTCAAATATTTGATGCTGTTTTTGAATGCACATTGAATATGATAAATAAGGACTTTGAAGAATATCCTGAACATAGAACGAACTTTTTCTTACTACTTCAGGCTGTCAATTCTCATTGTTTCCCAGCATTCCTTGCTATTCCACCTACACAGTTTAAACTTGTTTTGGATTCCATCATTTGGGCTTTCAAACATACTATGAGGAATGTCGCAGATACGGGCTTACAGATACTTTTTACACTCTTACAAAATGTTGCACAAGAAGAAGCTGCAGCTCAGAGTTTTTATCAAACTTATTTTTGTGATATTCTCCAGCATATCTTTTCTGTTGTGACAGACACTTCACATACTGCTGGTTTAACAATGCATGCATCAATTCTTGCATATATGTTTAATTTGGTTGAAGAAGGAAAAATAAGTACATCATTAAATCCTGGAAATCCAGTTAACAACCAAATCTTTCTTCAGGAATATGTGGCTAATCTCCTTAAGTCGGCCTTCCCTCACCTACAAGATGCTCAAGTAAAGCTCTTTGTGACAGGGCTTTTCAGCTTAAATCAAGATATTCCTGCTTTCAAGGAACATTTAAGAGATTTCCTAGTTCAAATAAAGGAATTTGCAGGTGAAGACACTTCTGATTTGTTTTTGGAAGAGAGAGAAATAGCCCTACGGCAGGCTGATGAAGAGAAACATAAACGTCAAATGTCTGTCCCTGGCATCTTTAATCCACATGAGATTCCAGAAGAAATGTGTGAT>SEQ ID NO: 69> ZBTB7AR247Q ; Length: 1752 nucleotidesATGGCCGGCGGCGTGGACGGCCCCATCGGGATCCCGTTCCCCGACCACAGCAGCGACATCCTGAGTGGGCTGAACGAGCAGCGGACGCAGGGCCTGCTGTGCGACGTGGTGATCCTGGTGGAGGGCCGCGAGTTCCCCACGCACCGCTCGGTGCTGGCCGCCTGCAGCCAGTACTTCAAGAAGCTGTTCACGTCGGGCGCCGTGGTGGACCAGCAGAACGTGTACGAGATCGACTTCGTCAGCGCCGAGGCGCTCACCGCGCTCATGGACTTCGCCTACACGGCCACGCTCACCGTCAGCACAGCCAACGTGGGTGACATCCTCAGCGCCGCCCGCCTGCTGGAGATCCCCGCCGTGAGCCACGTGTGCGCCGACCTCCTGGACCGGCAGATCCTGGCGGCCGACGCGGGCGCCGACGCCGGGCAGCTGGACCTTGT-149-4919-8127-7289.1Atty. Dkt. No.: 121384-0284AGATCAAATTGATCAGCGCAACCTCCTCCGCGCCAAGGAGTACCTCGAGTTCTTCCAGAGCAACCCCATGAACAGCCTGCCCCCCGCGGCCGCCGCCGCCGCTGCCAGCTTCCCGTGGTCCGCCTTTGGGGCGTCCGATGATGACCTGGATGCCACCAAGGAGGCCGTGGCCGCCGCTGTGGCCGCCGTGGCCGCGGGCGACTGCAACGGCTTAGACTTCTATGGGCCGGGCCCCCCGGCCGAGCGGCCCCCGACGGGGGACGGGGACGAGGGCGACAGCAACCCGGGTCTGTGGCCAGAGCAGGATGAGGACGCCCCCACCGGGGGTCTCTTTCCGCCGCCGGTGGCCCCGCCGGCCGCCACGCAGAACGGCCACTACGGCCGCGGCGGAGAGGAGGAGGCCGCCTCGCTGTCGGAGGCGGCCCCCGAGCCGGGCGACTCTCCGGGCTTCCTGTCGGGAGCGGCCGAGGGCGAGGACGGGGACGGGCCCGACGTGGACGGGCTGGCGGCCAGCACGCTGCTGCAGCAGATGATGTCATCGGTGGGCCGGGCGGGGGCCGCGGCGGGGGACAGCGACGAGGAGTCGCGGGCCGACGACAAGGGCGTCATGGACTACTACCTGAAGTACTTCAGCGGCGCCCACGACGGCGACGTCTACCCGGCCTGGTCGCAGAAGGTGGAGAAGAAGATCCGAGCCAAGGCCTTCCAGAAGTGCCCCATCTGCGAGAAGGTCATCCAGGGCGCCGGCAAGCTGCCGCGACACATCCGCACCCACACGGGCGAGAAGCCCTACGAGTGCAACATCTGCAAGGTCCGCTTCACCAGGCAGGACAAGCTGAAGGTGCACATGCGGAAGCACACGGGCGAGAAGCCGTACCTGTGCCAGCAGTGCGGCGCCGCCTTTGCCCACAACTACGACCTGAAGAACCACATGCGCGTGCACACGGGCCTGCGCCCCTACCAGTGCGACAGCTGCTGCAAGACCTTCGTCCGCTCCGACCACCTGCACAGACACCTCAAGAAAGACGGCTGCAACGGCGTCCCCTCGCGCCGCGGCCGCAAGCCCCGCGTCCGGGGCGGGGCGCCCGACCCCAGCCCGGGGGCCACCGCGACCCCCGGCGCCCCCGCCCAGCCCAGCTCCCCCGACGCCCGGCGCAACGGCCAGGAGAAGCACTTTAAGGACGAGGACGAGGACGAGGACGTGGCCAGCCCCGACGGCTTGGGCCGGTTGAATGTAGCGGGCGCCGGTGGAGGAGGTGACAGCGGAGGTGGCCCCGGGGCCGCCACCGACGGTAACTTCACAGCCGGACTCGCC>SEQ ID NO: 70> ZFP36L1 K19N ; Length: 1752 nucleotidesATGACCACCACCCTCGTGTCTGCCACCATCTTCGACTTGAGCGAAGTTTTATGCAACGGTAACAAGATGCTCAACTATAGTGCTCCCAGTGCAGGGGGTTGCCTGCTGGACAGAAAGGCAGTGGGCACCCCTGCTGGTGGGGGCTTCCCTCGGAGGCACTCAGTCACCCTGCCCAGCTCCAAGTTCCACCAGAACCAGCTCCTCAGCAGCCTCAAGGGTGAGCCAGCCCCCGCTCTGAGCTCGCGAGACAGCCGCTTCCGAGACCGCTCCTTCTCGGAAGGGGGCGAGCGGCTGCTGCCCACCCAGAAGCAGCCCGGGGGCGGCCAGGTCAACTCCAGCCGCTACAAGACGGAGCTGTGCCGCCCCTTTGAGGAAAACGGTGCCTGTAAGTACGGGGACAAGTGCCAGTTCGCACACGGCATCCACGAGCTCCGCAGCCTGACCCGCCACCCCAAGTACAAGACGGAGCTGTGCCGCACCTTCCACACCATCGGCTTTTGCCCCTACGGGCCCCGCTGCCACTTCATCCACAACGCTGAAGAGCGCCGTGCCCTGGCCGGGGCCCGGGACCTCTCCGCTGACCGTCCCCGCCTCCAGCATAGCTTTAGCTTTGCTGGGTTTCCCAGTGCCGCTGCCACCGCCGCTGCCACCGGGCTGCTGGACAGCCCCACGTCCATCACCCCACCCCCTATTCTGAGCGCCGATGACCTCCTGGGCTCACCTACCCTGCCCGATGGCACCAATAACCCTTTTGCCTTCTCCAGCCAGGAGCTGGCAAGCCTCTTTGCCCCTAGCATGGGGCTGCCCGGGGGTGGCTCCCCGACC-150-4919-8127-7289.1Atty. Dkt. No.: 121384-0284ACCTTCCTCTTCCGGCCCATGTCCGAGTCCCCTCACATGTTTGACTCTCCCCCCAGCCCTCAGGATTCTCTCTCGGACCAGGAGGGCTACCTGAGCAGCTCCAGCAGCAGCCACAGTGGCTCAGACTCCCCGACCTTGGACAACTCAAGACGCCTGCCCATCTTCA GCAGACTTTCCATCTCAGATGACSEQ ID NO: 79RRAGC WT; Length 1197 nucleotidesATGTCCCTGCAGTACGGGGCGGAGGAGACGCCCCTCGCCGGCAGTTACGGCGCGGCCGATTCGTTTCCAAAGGACTTCGGCTACGGCGTGGAGGAGGAGGAAGAGGAGGCGGCGGCGGCGGGCGGAGGGGTTGGGGCAGGGGCAGGCGGTGGCTGTGGTCCGGGGGGCGCTGACAGCTCCAAGCCGAGGATTCTGCTCATGGGACTCCGGCGCAGCGGCAAGTCCTCCATCCAGAAGGTGGTGTTTCATAAGATGTCACCCAACGAGACCCTCTTTTTGGAAAGTACCAACAAGATTTATAAGGATGACATTTCCAATAGCTCCTTTGTGAATTTCCAGATATGGGATTTTCCTGGGCAAATGGACTTTTTTGACCCAACCTTTGACTATGAGATGATCTTCAGGGGAACAGGAGCATTGATATACGTCATTGACGCACAGGATGACTACATGGAGGCTTTAACAAGACTTCACATTACTGTTTCTAAAGCCTACAAAGTTAACCCAGACATGAATTTTGAGGTTTTTATTCACAAAGTTGATGGTCTGTCTGATGATCACAAAATAGAAACACAGAGGGACATTCATCAAAGGGCCAATGATGACCTTGCAGATGCTGGGCTAGAAAAACTCCATCTTAGCTTTTATCTGACTAGTATCTATGACCATTCAATATTTGAAGCCTTTAGTAAGGTGGTGCAGAAACTCATTCCACAACTGCCGACCTTGGAAAACCTATTAAATATCTTTATATCAAATTCAGGTATTGAAAAAGCTTTTCTCTTTGATGTTGTCAGCAAAATCTACATTGCAACAGACAGTTCCCCTGTGGATATGCAATCTTATGAACTTTGCTGTGACATGATCGATGTTGTAATTGATGTGTCTTGTATATATGGGTTAAAGGAAGATGGAAGTGGAAGTGCTTATGACAAAGAATCTATGGCAATTATCAAGCTGAATAATACAACTGTCCTTTATTTAAAGGAGGTGACTAAATTTTTGGCACTGGTCTGCATTCTAAGGGAAGAAAGCTTTGAAAGAAAAGGTTTAATAGACTACAACTTCCACTGTTTCCGAAAAGCTATTCATGAGGTTTTTGAGGTGGGTGTGACTTCTCACAGGAGCTGTGGTCACCAGACTAGTGCCTCCAGTCTGAAAGCGCTGACACACAATGGCACGCCACGAAACGCCATC> SEQ ID NO: 80> shAPI2-MALTl fusion; Length 2019 nucleotidesATGAATATTGTCGAGAACAGTATTTTCCTGTCTAACCTTATGAAATCTGCCAATACGTTTGAGCTGAAGTACGACCTGAGCTGTGAGCTTTATCGCATGTCTACCTATAGCACTTTTCCAGCGGGCGTACCTGTGAGCGAACGCTCTCTTGCCAGGGCCGGCTTCTATTACACAGGTGTGAACGATAAGGTCAAATGTTTTTGTTGTGGATTAATGCTGGACAACTGGAAAAGGGGAGACTCCCCTACCGAGAAGCATAAGAAACTGTACCCTAGTTGTAGGTTTGTACAATCACTGAACTCTGTGAATAACCTTGAGGCCACAAGTCAGCCTACGTTTCCCTCAAGTGTAACTAACTCTACACATAGCCTGTTACCAGGCACCGAAAATAGCGGCTACTTTCGAGGCAGTTACAGCAATTCACCATCCAACCCCGTGAATAGCAG-151-4919-8127-7289.1Atty. Dkt. No.: 121384-0284AGCCAACCAGGATTTCTCAGCCCTCATGAGAAGCAGCTACCATTGCGCAATGAAC AATGAAGAGCTGAACAACCTGGGCCACCCAGACAACAAGGAGCAGACTACTGAT CAGCCCCTGGCCAAAGACAAGGTGGCTCTTCTGATCGGCAACATGAATTACCGGG AGCACCCAAAGCTTAAAGCCCCATTGGTTGACGTCTACGAGCTGACCAATTTGCTT CGGCAACTCGACTTCAAAGTGGTGAGCCTGCTTGATCTGACTGAATATGAAATGA GAAATGCCGTGGATGAGTTTCTGCTGCTGCTGGACAAAGGTGTGTACGGGCTCCT GTACTATGCGGGACACGGCTATGAGAACTTCGGGAACTCCTTTATGGTTCCTGTCG ATGCACCTAATCCCTACCGGTCAGAGAATTGTCTTTGTGTGCAGAATATCTTAAAA CTGATGCAGGAAAAGGAGACCGGACTTAACGTGTTCCTGCTGGACATGTGTCGGA AGAGAAATGACTACGACGATACGATTCCTATCTTGGACGCCCTGAAGGTGACTGCT AATATCGTATTCGGATATGCGACCTGCCAAGGCGCTGAGGCTTTTGAGATACAGCA CAGCGGTTTGGCCAATGGAATCTTCATGAAGTTTCTCAAGGACAGGCTGCTGGAG GACAAGAAGATAACCGTGCTGCTTGACGAGGTTGCGGAGGACATGGGGAAATGTCACTTAACCAAGGGAAAGCAAGCCCTCGAAATTCGTTCTAGCCTGAGTGAGAAAC GCGCACTCACTGACCCAATTCAAGGAACTGAATACTCCGCAGAAAGTCTCGTACG CAACCTGCAGTGGGCTAAGGCACATGAGCTCCCGGAGAGTATGTGTCTGAAATTC GACTGTGGAGTGCAGATCCAGTTGGGATTTGCCGCTGAATTTAGCAACGTGATGAT CATCTATACCTCTATAGTCTACAAGCCCCCCGAGATCATTATGTGTGATGCATACGTA ACAGATTTCCCCCTTGACCTGGATATCGACCCCAAAGATGCCAACAAAGGAACAC CTGAAGAGACCGGGAGCTACTTGGTTAGCAAGGACCTCCCAAAACACTGTCTCTA CACAAGACTTTCCTCTCTCCAGAAGCTTAAGGAACATTTAGTCTTCACCGTCTGCC TTTCATACCAATACTCCGGACTTGAAGACACCGTGGAAGATAAGCAGGAGGTGAA CGTTGGCAAACCTCTGATTGCTAAACTGGACATGCATAGGGGGCTGGGCCGGAAA ACATGCTTCCAGACTTGTCTCATGAGCAACGGGCCCTACCAAAGCAGCGCTGCCA CTTCCGGAGGTGCAGGGCATTACCACTCTCTGCAGGATCCATTTCACGGCGTCTAT CACAGTCACCCCGGAAATCCCAGTAATGTCACACCAGCCGATTCCTGCCACTGTAGCAGAACTCCGGACGCCTTTATCTCAAGCTTCGCACACCATGCCAGCTGCCACTTT TCCAGATCTAACGTACCAGTTGAGACTACAGATGAAATCCCTTTTAGTTTCAGTGA CCGCTTAAGGATCAGCGAGAAA> SEQ ID NO: 81> RRAGC S75C; Length 1197 nucleotidesATGTCCCTGCAGTACGGGGCGGAGGAGACGCCCCTCGCCGGCAGTTACGGCGCGGCCGATTCGTTTCCAAAGGACTTCGGCTACGGCGTGGAGGAGGAGGAAGAGGAGGCGGCGGCGGCGGGCGGAGGGGTTGGGGCAGGGGCAGGCGGTGGCTGTGGTCCGGGGGGCGCTGACAGCTCCAAGCCGAGGATTCTGCTCATGGGACTCCGGCGCAGCGGCAAGTGCTCCATCCAGAAGGTGGTGTTTCATAAGATGTCACCCAACGAGACCCTCTTTTTGGAAAGTACCAACAAGATTTATAAGGATGACATTTCCAATAGCTCCTTTGTGAATTTCCAGATATGGGATTTTCCTGGGCAAATGGACTTTTTTGACCCAACCTTTGACTATGAGATGATCTTCAGGGGAACAGGAGCATTGATATACGTCATTGACGCACAGGATGACTACATGGAGGCTTTAACAAGACTTCACATTACTGTTTCTAAAGCCTACAAAGTTAACCCAGACATGAATTTTGAGGTTTTTATTCACAAAGTTGATGGTCTGTCTGATGATCACAAAATAGAAACACAGAGGGACATTCATCAAAGGGCCAATGATGACC-152-4919-8127-7289.1Atty. Dkt. No.: 121384-0284TTGCAGATGCTGGGCTAGAAAAACTCCATCTTAGCTTTTATCTGACTAGTATCTATGACCATTCAATATTTGAAGCCTTTAGTAAGGTGGTGCAGAAACTCATTCCACAACTGCCGACCTTGGAAAACCTATTAAATATCTTTATATCAAATTCAGGTATTGAAAAAGCTTTTCTCTTTGATGTTGTCAGCAAAATCTACATTGCAACAGACAGTTCCCCTGTGGATATGCAATCTTATGAACTTTGCTGTGACATGATCGATGTTGTAATTGATGTGTCTTGTATATATGGGTTAAAGGAAGATGGAAGTGGAAGTGCTTATGACAAAGAATCTATGGCAATTATCAAGCTGAATAATACAACTGTCCTTTATTTAAAGGAGGTGACTAAATTTTTGGCACTGGTCTGCATTCTAAGGGAAGAAAGCTTTGAAAGAAAAGGTTTAATAGACTACAACTTCCACTGTTTCCGAAAAGCTATTCATGAGGTTTTTGAGGTGGGTGTGACTTCTCACAGGAGCTGTGGTCACCAGACTAGTGCCTCCAGTCTGAAAGCGCTGACACACAATGGCACGCCACGAAACGCCATC>SEQ ID NO: 71>API2-MALT1 Fusion ; Length: 946 amino acidsMNIVENSIFLSNLMKSANTFELKYDLSCELYRMSTYSTFPAGVPVSERSLARAGFYYTGVNDKVKCFCCGLMLDNWKRGDSPTEKHKKLYPSCRFVQSLNSVNNLEATSQPTFPSSVTNSTHSLLPGTENSGYFRGSYSNSPSNPVNSRANQDFSALMRSSYHCAMNNENARLLTFQTWPLTFLSPTDLAKAGFYYIGPGDRVACFACGGKLSNWEPKDNAMSEHLRHFPKCPFIENQLQDTSRYTVSNLSMQTHAARFKTFFNWPSSVLVNPEQLASAGFYYVGNSDDVKCFCCDGGLRCWESGDDPWVQHAKWFPRCEYLIRIKGQEFIRQVQASYPHLLEQLLSTSDSPGDENAESSIIHFEPGEDHSEDAIMMNTPVINAAVEMGFSRSLVKQTVQRKILATGENYRLVNDLVLDLLNAEDEIREEERERATEEKESNELNNLGHPDNKEQTTDQPLAKDKVALLIGNMNYREHPKLKAPLVDVYELTNLLRQLDFKVVSLLDLTEYEMRNAVDEFLLLLDKGVYGLLYYAGHGYENFGNSFMVPVDAPNPYRSENCLCVQNILKLMQEKETGLNVFLLDMCRKRNDYDDTIPILDALKVTANIVFGYATCQGAEAFEIQHSGLANGIFMKFLKDRLLEDKKITVLLDEVAEDMGKCHLTKGKQALEIRSSLSEKRALTDPIQGTEYSAESLVRNLQWAKAHELPESMCLKFDCGVQIQLGFAAEFSNVMIIYTSIVYKPPEIIMCDAYVTDFPLDLDIDPKDANKGTPEETGSYLVSKDLPKHCLYTRLSSLQKLKEHLVFTVCLSYQYSGLEDTVEDKQEVNVGKPLIAKLDMHRGLGRKTCFQTCLMSNGPYQSSAATSGGAGHYHSLQDPFHGVYHSHPGNPSNVTPADSCHCSRTPDAFISSFAHHASCHF SRSNVPVETTDEIPF SFSDRLRISEK> SEQ ID NO: 82> shAPI2-MALTl fusion; Length 673 amino acidsMNIVENSIFLSNLMKSANTFELKYDLSCELYRMSTYSTFPAGVPVSERSLARAGFYYT GVNDKVKCFCCGLMLDNWKRGDSPTEKHKKLYPSCRFVQSLNSVNNLEATSQPTFP S S VTNSTHSLLPGTENSGYFRGS YSNSPSNPVNSRANQDF S ALMRS S YHCAMNNEEL NNLGHPDNKEQTTDQPLAKDKVALLIGNMNYREHPKLKAPLVDVYELTNLLRQLDF KVVSLLDLTEYEMRNAVDEFLLLLDKGVYGLLYYAGHGYENFGNSFMVPVDAPNPYRSENCLCVQNILKLMQEKETGLNVFLLDMCRKRNDYDDTIPILDALKVTANIVFGYA-153-4919-8127-7289.1Atty. Dkt. No.: 121384-0284TCQGAEAFEIQHSGLANGIFMKFLKDRLLEDKKITVLLDEVAEDMGKCHLTKGKQALEIRSSLSEKRALTDPIQGTEYSAESLVRNLQWAKAHELPESMCLKFDCGVQIQLGFAAEFSNVMIIYTSIVYKPPEIIMCDAYVTDFPLDLDIDPKDANKGTPEETGSYLVSKDLPKHCLYTRLSSLQKLKEHLVFTVCLSYQYSGLEDTVEDKQEVNVGKPLIAKLDMHRGLGRKTCFQTCLMSNGPYQSSAATSGGAGHYHSLQDPFHGVYHSHPGNPSNVTPADSCHCSRTPDAFISSFAHHASCHFSRSNVPVETTDEIPFSFSDRLRISEK> SEQ ID NO: 72> MYC wild-type; Length: 454 amino acidsMDFFRVVENQQPPATMPLNVSFTNRNYDLDYDSVQPYFYCDEEENFYQQQQQSELQ PPAPSEDIWKKFELLPTPPLSPSRRSGLCSPSYVAVTPFSLRGDNDGGGGSFSTADQLE MVTELLGGDMVNQ SFICDPDDETFIKNIIIQDCMWSGF S AAAKLVSEKL AS YQ AARK DSGSPNPARGHSVCSTSSLYLQDLSAAASECIDPSVVFPYPLNDSSSPKSCASQDSSAF SPSSDSLLSSTESSPQGSPEPLVLHEETPPTTSSDSEEEQEDEEEIDVVSVEKRQAPGKR SESGSPSAGGHSKPPHSPLVLKRCHVSTHQHNYAAPPSTRKDYPAAKRVKLDSVRVL RQISNNRKCTSPRSSDTEENVKRRTHNVLERQRRNELKRSFFALRDQIPELENNEKAP KVVILKKATAYILSVQAEEQKLISEEDLLRKRREQLKHKLEQLRNSCA> SEQ ID NO: 73> mCXCR4 S345X ; Length: 341 amino acidsMEPISVSIYTSDNYSEEVGSGDYDSNKEPCFRDENVHFNRIFLPTIYFIIFLTGIVGNGLVILVMGYQKKLRSMTDKYRLHLSVADLLFVITLPFWAVDAMADWYFGKFLCKAVHIIYTVNLYSSVLILAFISLDRYLAIVHATNSQRPRKLLAEKAVYVGVWIPALLLTIPDFIFADVSQGDISQGDDRYICDRLYPDSLWMVVFQFQHIMVGLILPGIVILSCYCIIISKLSHSKGHQKRKALKTTVILILAFFACWLPYYVGISIDSFILLGVIKQGCDFESIVHKWISITEALAFFHCCLNPILYAFLGAKFKS S AQHALNSMSRGS SLKILSKGKR> SEQ ID NO: 74> mIL4R L243N ; Length: 810 amino acidsMGRLCTKFLTSVGCLILLLVTGSGSIKVLGEPTCFSDYIRTSTCEWFLDSAVDCSSQLC LHYRLMFFEFSENLTCIPRNSASTVCVCHMEMNRPVQSDRYQMELWAEHRQLWQGS FSPSGNVKPLAPDNLTLHTNVSDEWLLTWNNLYPSNNLLYKDLISMVNISREDNPAEF IVYNVTYKEPRLSFPINILMSGVYYTARVRVRSQILTGTWSEWSPSITWYNHFQLPLIQ RLPLGVTISCNCIPLFCLFCYFSITKIKKIWWDQIPTPARSPLVAIIIQDAQVPLWDKQTR SQESTKYPHWKTCLDKLLPCLLKHRVKKKTDFPKAAPTKSLQSPGKAGWCPMEVSRTVLWPENVSVSVVRCMELFEAPVQNVEEEEDEIVKEDLSMSPENSGGCGFQESQADI-154-4919-8127-7289.1Atty. Dkt. No.: 121384-0284MARLTENLFSDLLEAENGGLGQSALAESCSPLPSGSGQASVSWACLPMGPSEEATCQ VTEQPSHPGPLSGSPAQSAPTLACTQVPLVLADNPAYRSFSDCCSPAPNPGELAPEQQQ ADHLEEEEPPSPADPHSSGPPMQPVESWEQILHMSVLQHGAAAGSTPAPAGGYQEFV QAVKQGAAQDPGVPGVRPSGDPGYKAFSSLLSSNGIRGDTAAAGTDDGHGGYKPFQ NPVPNQSPSSVPLFTFGLDTELSPSPLNSDPPKSPPECLGLELGLKGGDWVKAPPPADQ VPKPFGDDLGFGIVYSSLTCHLCGHLKQHHSQEEGGQSPIVASPGCGCCYDDRSPSLG SLSGALESCPEGIPPEANLMSAPKTPSNLSGEGKGPGHSPVPSQTTEVPVGALGIAVS> SEQ ID NO: 75> mPDCDl ; Length: 288 amino acidsMWVRQVPWSFTWAVLQLSWQSGWLLEVPNGPWRSLTFYPAWLTVSEGANATFTCSLSNWSEDLMLNWNRLSPSNQTEKQAAFCNGLSQPVQDARFQIIQLPNRHDFHMNILDTRRNDSGIYLCGAISLHPKAKIEESPGAELVVTERILETSTRYPSPSPKPEGRFQGMVIGIMSALVGIPVLLLLAWALAVFCSTSMSEARGAGSKDDTLKEEPSAAPVPSVAYEELDFQGREKTPELPTACVHTEYATIVFTEGLGASAMGRRGSADGLQGPRPPRHEDGHCSWPL> SEQ ID NO: 76> tCD19 ; Length: 317 amino acidsMPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWHWLLRTGGWKVSAVTLAYLIFCLCSLVGILHLQRAL> SEQ ID NO: 77> tCD20 ; Length: 290 amino acidsMTTPRNSVNGTFPAEPMKGPIAMQSGPKPLFRRMSSLVGPTQSFFMRESKTLGAVQIMNGLFHIALGGLLMIPAGIYAPICVTVWYPLWGGIMYIISGSLLAATEKNSRKCLVKGKMIMNSLSLFAAISGMILSIMDILNIKISHFLKMESLNFIRAHTPYINIYNCEPANPSEKNSPSTQYCYSIQSLFLGILSVMLIFAFFQELVIAGIVENEWKRNIVLLSAEEKKEQTIEIKEEVVGLTETSSQPKNEEDIEIIPIQEEEEEETETNFPEPPQDQESSPIENDSSP> SEQ ID NO: 78-155-4919-8127-7289.1Atty. Dkt. No.: 121384-0284> F0XP1 wild-type; Length: 694 amino acidsMMQESGTETKSNGSAIQNGSGGSNHLLECGGLREGRSNGETPAVDIGAADLAHAQQ QQQQALQVARQLLLQQQQQQQVSGLKSPKRNDKQPALQVPVSVAMMTPQVITPQQ MQQILQQQVLSPQQLQVLLQQQQALMLQQQQLQEFYKKQQEQLQLQLLQQQHAGK QPKEQQQVATQQLAFQQQLLQMQQLQQQHLLSLQRQGLLTIQPGQPALPLQPLAQG MIPTELQQLWKEVTSAHTAEETTGNNHSSLDLTTTCVSSSAPSKTSLIMNPHASTNGQ LSVHTPKRESLSHEEHPHSHPLYGHGVCKWPGCEAVCEDFQSFLKHLNSEHALDDRS TAQCRVQMQVVQQLELQLAKDKERLQAMMTHLHVKSTEPKAAPQPLNLVSSVTLS KSASEASPQSLPHTPTTPTAPLTPVTQGPSVITTTSMHTVGPIRRRYSDKYNVPISSADI AQNQEFYKNAEVRPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNAATWK GAIRTNLSLHKCFIRVEDEFGSFWTVDDEEFKRGRHIQRGRPRKYCPDENFDELVAHN PSLIKNMQSSHAYCTPLNAALQASMAENSIPLYTTASMGNPTLGNLASAIREELNGAM EHTNSNESDSSPGRSPMQAVHPVHVKEEPLDPEEAEGPLSLVTTANHSPDFDHDRDYE DEPVNEDME*Equivalents

[0296] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs.

[0297] Although the foregoing refers to particular preferred embodiments, it will be understood that the present invention is not so limited. It will occur to those of ordinary skill in the art that various modifications may be made to the disclosed embodiments and that such modifications are intended to be within the scope of the present invention.

[0298] The present technology illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising,” “including,” “containing,” etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the present technology claimed.

[0299] Thus, it should be understood that the materials, methods, and examples provided here are representative of preferred aspects, are exemplary, and are not intended as limitations on the scope of the present technology.-156-4919-8127-7289.1Atty. Dkt. No.: 121384-0284[03001 The present technology has been described broadly and generically herein. Each of the narrower species and sub-generic groupings falling within the generic disclosure also form part of the present technology. This includes the generic description of the present technology with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

[0301] In addition, where features or aspects of the present technology are described in terms of Markush groups, those skilled in the art will recognize that the present technology is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0302] All publications, patent applications, patents, GenBank citations, ATCC citations, and other references mentioned herein are expressly incorporated by reference in their entirety, to the same extent as if each were incorporated by reference individually. In case of conflict, the specification, including definitions, will control.-157-4919-8127-7289.1

Claims

Atty. Dkt. No.: 121384-0284WHAT IS CLAIMED IS:

1. A vector comprising a nucleic acid sequence encoding a polypeptide selected from a) a B cell lymphoma wild-type protein or functional fragment thereof, or b) a B cell lymphoma mutant protein or functional fragment thereof, wherein the T cell lymphoma mutant protein or functional fragment thereof is a variant of the wild-type protein or functional fragment thereof.

2. The vector of claim 1, wherein the variant comprises a single-point, double-point, insertion, or fusion mutation of the wild-type protein.

3. The vector of claim 1 or 2, wherein the vector is selected from a plasmid, a herpes simplex virus, a retrovirus, an adenovirus, or an adeno-associated virus.

4. The vector of claim 3, wherein the retrovirus is a lentivirus.

5. The vector of any of claims 1-4, wherein the protein is selected from a variant in Tables 1 or 5.

6. The vector of any of claims 1-4, wherein the variant or wild-type protein is selected from a: BCL10 substitution at amino acid 58, 140, or 209; BCL10 wild-type; CTSS substitution at amino acid 132; ShAPI2-MALTl fusion; HNRNPD substitution at amino acid 48; FOXO1 substitution at amino acid 24; MEF2C substitution at amino acid 389;HIST1H1E substitution at amino acid 158; IRF8 substitution at amino acid 23; HRAS substitution at amino acid 145; MEF2B substitution at amino acid 83; BTK substitution at amino acid 474 and 513; IKBKB substitution at amino acid 171; BCL2 substitution at amino acid 7 or 33; CARD11 substitution at amino acid 49; MYD88 substitution at amino acid 265; KLF2 substitution at amino acid 291; MYC-IGH / MYC fusion; PIK3CD substitution at amino acid 1021; PIM2 substitution at amino acid 27 or 31; MAP2K1 substitution at amino acid 53; OSBPLIO substitution at amino acid 94; IGH-FOXP1 / FOXP1 fusion; TNRFSF14 substitution at amino acid 135; CD79B substitution at amino acid 196; HIST1H2BC substitution at amino acid 63; STAT6 substitution at amino acid 419; SGK1 substitution at amino acid 143; RRAGC substitution at amino acid 90; RRAGC wild-type; EGR1-158-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 substitution at amino acid 34; ATP6V1B2 substitution at amino acid 371 or 400; BTG1 substitution at amino acid 36; CXCR4 wild-type; DIS3 substitution at amino acid 488; ETNK1 substitution at amino acid 244; ETS1 substitution at amino acid 23; EZH2 substitution at amino acid 113 or 646; HIST1H1D substitution at amino acid 186; IKZF3 substitution at amino acid 162; IRF4 substitution at amino acid 66; KLHL6 substitution at amino acid 90; MAP2K2 substitution at amino acid 60; mCXCR4 substitution at amino acid 345; mIL4R substitution at amino acid 243; mPDCDl wild-type; MYD88 wild-type; NKAP substitution at amino acid 405; PIM1 substitution at amino acid 81; PIM2 substitution at amino acid 31; PPP4C substitution at amino acid 54; PTPN11 wild-type; RFTN1 substitution at amino acid 255; SOCS1 substitution at amino acid 17; TBL1XR1 substitution at amino acid 446 or wild-type; tCD19 wild-type; tCD20 wild-type; TLR2 substitution at amino acid 327; USP8 substitution at amino acid 657; XPO1 wild-type; ZBTB7A substitution at amino acid 247; MYC wild-type; FOXP1 wild-type; and / or ZFP36L1 substitution at amino acid 19.

7. The vector of any of claims 1-4, wherein the vector comprises a nucleic acid sequence selected from SEQ ID NOs: 1-70, 79-81.

8. An engineered cell comprising the vector of any of claims 1-7.

9. An engineered cell comprising: a) at least one nucleic acid comprising a sequence selected from SEQ ID NOs: 1-70, 79-81; or b) at least one polypeptide encoded by a sequence selected from SEQ ID NOs: 1-70, 79-81.

10. The engineered cell of claim 8 or 9, wherein the engineered cell is a T cell.

11. The engineered cell of claim 10, wherein the T cell is selected from a CAR T cell, CD3+ cell, CD8+ cell, CD4+ cell, regulatory T cell, a gamma delta T cell (yST), an invariant natural killer T (iNKT) cell, a mucosal associated invariant T (MAIT) cell, a macrophage, a monocyte, a natural killer (NK) cell, a tumor infiltrating lymphocyte (TIL), a cytotoxic T cell, a T helper cell, a memory T cell, a central memory T (TCM) cell, a stem memory T (TSCM)-159-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 cell, a stem-cell-like memory T cell (or stem-like memory T cells), an effector memory T (TEM) cell, a TEMRA (CD45RA+) cell, an effector T cell, a Thl cell, a Th2 cell, a Th9 cell, a Th 17 cell, a Th22 cell, a Tfh (follicular helper) cell, a natural killer T (NKT) cell, a transitional memory T (TTM) cell, a terminal effector T (TTE) cell, or a naive T (TN) cell.

12. The engineered cell of any of claims 8-11, wherein the T cell comprises a receptor with specificity for a target antigen.

13. The engineered cell of claim 12, wherein the target antigen is selected from CD19, B7H3 (CD276), BCMA (CD269), ALPPL2, Claudin 18.2, CD123, CD171, CD179a, CD20, CD213A2, CD22, CD24, CD246, CD272, CD30, CD33, CD38, CD44v6, CD46, CD71, CD97, CEA, Claudin 6(CLDN6), CLECL1, CS-1, DLL-3, EGFR, EGFRvIII, ELF2M, EpCAM, EphA2, Ephrin B2, FAP, FLT3, GCC, GD2, GD3, GM3, GPRC5D, HER2 (ERBB2 / neu), IGLL1, IL-llRa, KIT (CD 117), KLK2, LY6G6D, MUC1, NCAM, p53R175H, PAP, PDGFR-P, PRAME, PRSS21, PSCA, PSMA, R0R1, SIRPa, SSEA-4, TAG72, TEM1 / CD248, TEM7R, TSHR, VEGFR2, ALPI, citrullinated vimentin, cMet, and / or Axl.

14. The engineered cell any of claims 12-13, wherein the target antigen is selected from cell surface receptors, adhesion proteins, integrins, mucins, lectins, tumor-associated antigens, and tumor-specific antigens.

15. The engineered cell of any of claims 8-14, wherein the engineered cell has increased or decreased signaling through the API, NF AT, NFKB, and / or PD1 pathways compared to a cell of the same type without the nucleic acid or polypeptide.

16. The engineered cell of any of claims 8-15, wherein the engineered cell has increased or decreased cytokine production compared to a cell of the same type without the nucleic acid or polypeptide.

17. The engineered cell of claim 16, wherein the cytokine is selected from IL-2, IL-4, II- 5, TNF alpha, IFN- gamma and / or IL-13.-160-4919-8127-7289.1Atty. Dkt. No.: 121384-028418. A composition comprising the engineered cell of any of claims 8-17 and a pharmaceutically acceptable carrier.

19. A method to increase the persistence of T cells in a cancer cell, comprising contacting the tumor with the engineered cell of any of claims 8-17 or the composition of claim 18.

20. A method to increase the persistence of T cells in a tumor, comprising contacting the tumor with the engineered cell of any of claims 8-17 or the composition of claim 18.

21. The method of claim 20, wherein the contacting in in vivo or in vitro.

22. A method to increase the persistence of T cells in a tumor microenvironment or tumor draining lymph nodes of a subject in need thereof, comprising administering to the subject in the engineered cell of any of claims 8-17 or the composition of claim 18.

23. A method to prevent tumor recurrence in a subj ect in need thereof, comprising administering to the subject in need the engineered cell of any of claims 8-17 or the composition of claim 18 after a subject has reduced tumor growth or symptoms, optionally wherein the subject is in remission.

24. A method to inhibit the growth of a cancer and / or increase the survival rate of a subject, in need, comprising administering to the subject in with the engineered cell of any of claims 8-17 or the composition of claim 18.

25. The method of any of claims 22-24, wherein the cancer is a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.

26. The method of any of claims 22-24, wherein the cancer is a solid tumor.-161-4919-8127-7289.1Atty. Dkt. No.: 121384-028427. A method to inhibit the growth of a first cancer and / or increase the survival rate of a subject in need, comprising administering to the subject in with the engineered cell of any of claims 8-17 or the composition of claim 18, wherein growth of a second cancer is also inhibited after the first tumor is contacted with the engineered cell or composition, and wherein the first cancer comprises an antigen recognized by the engineered cell.

28. The method of claim 27 wherein the first and the second cancer are the same or different.

29. The method of claim 27 or 28, wherein the second cancer is negative for the T-cell dependent antigen.

30. The method of any of claims 27-29, wherein the first cancer and / or second cancer is a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.31 . The method of any of 27-29, wherein the first cancer is a tumor, and further optionally wherein the second cancer is a tumor.

32. The method of any of claims 23-31, wherein the administration is parenteral (including intramuscular, subcutaneous, intradermal, intravascular, intravenous, intraarterial, intramedullary and intrathecal), intraperitoneal, or intratumoral.

33. The method of any of claims 23-31, wherein the subject in need is a mammal, optionally a human.

34. A method to generate a vector, comprising transferring a plasmid to a cell, wherein the plasmid comprises a nucleotide encoding a polypeptide comprising at least one B cell lymphoma mutant protein or functional fragment thereof, wherein the T cell lymphoma-162-4919-8127-7289.1Atty. Dkt. No.: 121384-0284 mutant protein or functional fragment thereof is a variant of the wild-type protein or functional fragment thereof.

35. The method of claim 34, wherein the variant or wild-type protein is selected from a: BCL10 substitution at amino acid 58, 140, or 209; BCL10 wild-type; CTSS substitution at amino acid 132; ShAPI2-MALTl fusion; API2-MALT1 fusion; HNRNPD substitution at amino acid 48; FOXO1 substitution at amino acid 24; MEF2C substitution at amino acid 389; HIST1H1E substitution at amino acid 158; IRF8 substitution at amino acid 23; HRAS substitution at amino acid 145; MEF2B substitution at amino acid 83; BTK substitution at amino acid 474 and 513; IKBKB substitution at amino acid 171; BCL2 substitution at amino acid 7 or 33; CARD11 substitution at amino acid 49; MYD88 substitution at amino acid 265; KLF2 substitution at amino acid 291; MYC-IGH / MYC fusion; PIK3CD substitution at amino acid 1021; PIM2 substitution at amino acid 27 or 31; MAP2K1 substitution at amino acid 53; OSBPLIO substitution at amino acid 94; IGH-FOXP1 / FOXP1 fusion; TNRFSF14 substitution at amino acid 135; CD79B substitution at amino acid 196; HIST1H2BC substitution at amino acid 63; STAT6 substitution at amino acid 419; SGK1 substitution at amino acid 143; RRAGC substitution at amino acid 90; RRAGC wild-type; EGR1 substitution at amino acid 34; ATP6V1B2 substitution at amino acid 371 or 400; BTG1 substitution at amino acid 36; CXCR4 wild-type; DIS3 substitution at amino acid 488; ETNK1 substitution at amino acid 244; ETS1 substitution at amino acid 23; EZH2 substitution at amino acid 113 or 646; HIST1H1D substitution at amino acid 186; IKZF3 substitution at amino acid 162; IRF4 substitution at amino acid 66; KLHL6 substitution at amino acid 90; MAP2K2 substitution at amino acid 60; mCXCR4 substitution at amino acid 345; mIL4R substitution at amino acid 243; mPDCDl wild-type; MYD88 wild-type; NKAP substitution at amino acid 405; PIM1 substitution at amino acid 81; PIM2 substitution at amino acid 31; PPP4C substitution at amino acid 54; PTPN11 wild-type; RFTN1 substitution at amino acid 255; SOCS1 substitution at amino acid 17; TBL1XR1 substitution at amino acid 446 or wild-type; tCD19 wild-type; tCD20 wild-type; TLR2 substitution at amino acid 327; USP8 substitution at amino acid 657; XPO1 wild-type; ZBTB7A substitution at amino acid 247; MYC wild-type; FOXP1 wild-type and / or ZFP36L1 substitution at amino acid 19.-163-4919-8127-7289.1Atty. Dkt. No.: 121384-028436. The method of claim 34, wherein the nucleotide comprises a sequence according to at least one of SEQ ID NO: 1-70, 79, or 80.

37. The method of any of claims 34-36, wherein the vector is a retrovirus, optionally a lentivirus.

38. A kit comprising optional instructions for use and one or more of the following: a vector of any one of claims 1-7, an engineered cell of any one of claims 8-17, or the composition of claim 19.-164-4919-8127-7289.1