32 results about "Homologous Recombination Deficiency" patented technology

The invention discloses a method for predicating a homologous recombination deficiency (HRD) mechanism and a method for predicating response of patients to cancer therapy and relates to the field of biological information predication. The method comprises the step of judging whether a tumor sample has homologous recombination deficiency or not according to one or more comprehensive values in a large-segment INDEL (Insertion/Deletion) fraction, a copy number variation fraction and a tumor mutation load fraction, wherein the comprehensive values can also comprise a loss of heterozygosity variation fraction. By adopting the method disclosed by the invention, predication of a chromosome large-segment structure, a chromosome gene type number, a chromosome gene copy number, a chromosome variation interval and abnormal loss of heterozygosity and chromosome telomeric imbalance is realized, so that an evaluation range is more complete and HRD can be accurately predicated; the comprehensive values also can be used for determining whether the patients have response to a therapeutic regimen containing one or more of a PARP (Poly Adenosine Diphosphate Ribose Polymerase) inhibitor, an DNA (Deoxyribonucleic Acid) injury inhibitor, a topoisomerase II/II+inhibitor, a topoisomerase I inhibitor and radiotherapy; the method is simple and has wide general applicability.

A single-sample whole-genome allele specific copy number variation prediction method comprises the following steps: analyzing and comparing sequencing data of a to-be-detected sample to a reference genome, and extracting tumor purity information, whole-genome replication information and total copy number variation information; performing classification processing according to the total copy number variation information of each segment of the chromosome, converting the total copy number variation information into allele specific copy number variation information, if the total copy number variation information of the chromosome segment is an odd number interval or a zero interval, directly calculating the allele specific copy number variation information, and if the total copy number variation information of the chromosome segment is an odd number interval or a zero interval, directly calculating the allele specific copy number variation information; and if the total copy number variation information of the chromosome segment is a non-zero even interval, obtaining allele specific copy number variation information of the interval through model prediction. According to the method, only a single sample is needed, a normal sample does not need to be paired, the sequencing depth of the needed to-be-detected sample is low, the detection accuracy is high, and the homologous recombination defect of the low-tumor-purity sample can be detected.

The invention relates to a method and a test kit for determining genome instability on the basis of a next-generation sequencing technology, belonging to the technical field of molecular detection. Inorder to overcome the defect that genome structure variation is not considered during detection of homologous recombination defects in the prior art, the invention provides the method and the test kit for determining genome instability on the basis of the next-generation sequencing technology. The method comprises the following steps: breaking a to-be-detected gene, then adding an A connector fora corresponding PCR reaction, carrying out hybridization capture through a designed probe, then amplifying a captured DNA library, sequencing the library, and carrying out evaluating through a software so as to determine the homologous recombination defect state. Compared with the prior art, the method provided by the invention can comprehensively evaluate the HRD state, is reliable in data results and is applicable to popularization.

This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of homologous recombination deficiency (HRD) or an HRD signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an HRD signature are provided. Materials and methods for identifying cells (e.g., cancer cells) having a deficiency in homology directed repair (HDR) as well as materials and methods for identifying cancer patients likely to respond to a particular cancer treatment regimen also are provided.

The invention discloses an HRD score calculation method based on chip detection. The HRD score calculation method comprises the specific operation steps: 1, establishing a genome heterozygosity deletion LOH calculation method; 2, establishing a calculation method of the telomere allele imbalance TAI; 3, establishing a calculation method of large chip end migration LST; 4, establishing an HRD calculation method. The invention provides a genome heterozygosity deletion LOH calculation method, a telomere allelic imbalance TAI calculation method, a large fragment end migration LST calculation method and an HRD calculation method, which can perform HRD score calculation on paraffin samples, and can evaluate HRD of tumor tissues by combining data of an Affymetrix OncoScan CNV FFPE gene chip withan HRD evaluation method; and the homologous recombination defect state of the detected tumor sample can be more accurately judged through the HRD score.

Described herein are methods, systems, devices and computer program products for characterizing or identifying a type of cancer. Also described are methods of treating a characterized or identified chancer. For example, certain methods may be used to characterize a homologous recombination deficiency status of a cancer.

The invention relates to a novel method for identifying homologous recombination deficiency and application thereof. More particularly, the present invention relates to a characteristic genome recombination fingerprint which is related to hHRD type homologous recombination repair deficiency and is resolved by using high throughput genome re-sequencing, bioinformatics analysis and statistical correlation analysis. The characteristic hHRD recombination fingerprint is caused by the functional deficiency of a specific homologous recombination repair mechanism (namely CRL4WDR70-H2B mono-ubiquitination pathway), and comprises the total frequency of genome recombination in a single sample, the composition of chromosome structure variation types and site-specific copy number variation. The recombinant fingerprint is used for identifying infectious diseases or tumors with the characteristic mutant fingerprint, and is used for guiding targeted drug treatment of PARP inhibitors. The invention relates to the method and application thereof for diseases including but not limited to breast cancer, ovarian cancer, endometrial (like) cancer, ovarian clear cell cancer, prostate cancer, pancreatic cancer, skin cancer and gastric cancer with such characteristics, as well as hepatitis B virus infection or related liver fibrosis cirrhosis, liver cancer and cholangiocarcinoma.

The present invention discloses a genomic characteristic mutation fingerprint related to hHRD type homologous recombination repair defects and comprises a combination characteristic of a single nucleotide variation (SNV) and insertion deletion (Indel) genomic fingerprint, and an identification method thereof. The fingerprint characteristics can be subjected to high-throughput whole-genome resequencing, bioinformatics software analysis and statistical correlation analysis and are used to identify infectious diseases or tumors with the characteristic mutation fingerprints, especially hepatitis Bvirus infection and related diseases, including liver cirrhosis, liver fibrosis and liver cancer. The mutation fingerprint can also be used to guide methods and uses of treatments of targeted drugs targeting the homologous recombination defects on a variety of the various tumors with the hHRD homologous recombination repair defects, including but not limited to breast cancer, ovarian cancer, endometrial cancer, endometrioid carcinoma, ovarian clear cell carcinoma, prostate cancer, gastric cancer, skin cancer, hepatitis B virus infection or related liver cirrhosis, liver cancer and bile duct cell cancer.

Methods for sorting out cancer sub-types based on sensitivity to DNA damaging drugs or inhibitors of DNA repair are described so that patients can be selected as candidates for treatment with these agents.

The invention relates to the field of grading detection of tumors, in particular to application of a gene combination to preparation of products for grading detection of human tumor homologous recombination defects, tumor mutation loads and microsatellite instability, and the gene combination is composed of a gene set A and a gene fragment set B, the gene combination is obtained from actual high-throughput sequencing data of a first hospital of Beijing University through specific pairing clustering analysis, the data from the real world has higher reliability and credibility, and homologous recombination defect, tumor mutation load and microsatellite instability grading and prediction can be accurately carried out on the pan cancer.

The invention discloses a method and device for correcting a homologous recombination defect score and a storage medium. The method comprises the following steps that: a system CNV and a system SNV of a to-be-detected sample are acquired; a WGD value, an original LOH score value, an original TAI score value and an original LST score value of the to-be-detected sample under an optimal model are calculated by utilizing system CNV and system SNV; and for the to-be-detected sample subjected to WGD, the corrected LST score value is equal to the product of (1-k1* WGD value) and the original LST score value, and the corrected TAI score value is equal to the product of (1-k2 * WGD value) and the original LST score value. According to the method and the device for correcting the homologous recombination defect score, the TAI and the LST are corrected by using the WGD value, so that the problem that TAI and LST scores of a whole genome multiplication sample are relatively high is solved, and the sensitivity and the accuracy of homologous recombination defect state evaluation are improved.

The invention relates to the field of biomedicine, in particular to a method for predicting ovarian cancer homologous recombination defects based on a genome copy number variation biomarker and application. The biomarker is a CNV based on any one of a chromosome segment 5q13. 2, a chromosome segment 8q24.2 or a chromosome segment 19q12. The method for predicting the ovarian cancer homologous recombination defect by using the biomarker comprises the following steps of, collecting an operation excision sample or a tissue biopsy sample of an ovarian cancer patient; performing DNA sequencing on the sample to obtain a corresponding sequencing file; analyzing the DNA sequencing file by using GISTIC 2.0 to obtain a CNV map of a tumor whole genome; and predicting HRD status of ovarian cancer based on the CNV of the chromosome segment 5q13.2, 8q24.2 or 19q12. The invention provides the application of the copy number variation CNV at the subchromosome and gene level in predicting the homologous recombination defect of the ovarian cancer patient, so that potential benefit people of targeted therapy are screened, and more clinical benefits are brought to the HRD patient.

The invention concerns compositions and a method for treating or delaying the onset, progression, or relapse of a cancer in a subject, the method comprising administering, optionally with radiation therapy, an inhibitor of: (a) DNA-Dependent Protein Kinase catalytic subunit, and an inhibitor of Poly-ADP Ribose Polymerase, wherein the cancer has a histone H3.3 mutation or is a homologous recombination-defective (HR-defective) cancer; or (b) wild-type isocitrate dehydrogenase, wherein the IDH inhibitor is administered in an effective amount to decrease wild-type IDH activity in cells of the cancer, and wherein the cancer carries a histone H3.3 K27M mutation, and/or the cancer has low DNA methylation and/or low histone methylation; or (c) histone acetyltransferase, wherein the cancer carries a histone H3.3 K27M mutation, and/or high histone acetylation; or (d) histone deacetylase, wherein the cancer carries a histone H3.3 K27M mutation, and/or has high histone acetylation; or (e) any combination thereof.

Disclosed herein are certain acetamido derivatives that are DNA Polymerase Theta (Polθ) inhibitors of Formula (I). Also, disclosed are pharmaceutical compositions comprising such compounds and methods of treating diseases treatable by inhibition of Polθ such as cancer, including homologous recombination (HR) deficient cancers.