59 results about "Heterozygosity Loss" patented technology

Methods for estimating genomic copy number and loss of heterozygosity using Hidden Markov Model based estimation are disclosed.

The present invention relates to a novel method for the amplification of DNA, this method being particularly useful for the amplification of the DNA or the whole genome of a single cell, chromosomes or fragments thereof. Described is also the use of the method in DNA analysis for medical, forensic, diagnostic or scientific purposes, like comparative genomic hybridization (CGH)-, fluorescence in situ hybridization (FISH)-, polymerase chain reaction (PCR)-, single strand conformation polymorphism (SSCP)-, DNA sequence-, "loss of heterozygosity" (LOH)-, fingerprint- and/or restriction fragment length polymorphism (RFLP)-analysis.

A method is provided for assessing allelic losses on specific chromosomal regions in melanoma patents. The method relies on the evidence that free DNA may be released in the plasma/serum of cancer patients allowing the detection of DNA with LOH in the plasma/serum of cancer patients by analysis for microsatellite markers. The amount of and specific allelic loss allows a prognosis to be made regarding tumor diagnosis and progression, tumor metastasis, tumor recurrence, and mortality.

The invention relates to fields of use of unlabelled polynucleotide probes able to form hairpins, the biochips comprising such probes and methods allowing use thereof. The present invention also concerns methods for designing such probes and biochips. More particularly, the invention concerns the use of such unlabelled probes and biochips for manipulating and analysing polynucleotide sequences and optionally molecules which are associated therewith. This invention further concerns methods for preparing and use such probes and biochips for analysing mutations, sequencing, detection of alternative splicing variants, gene expression analysis, analysis of allelic imbalances and loss of heterozygosity and the detection of any nucleic acid present in organisms or residues from said organisms.

This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of a loss of heterozygosity (LOH) signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an LOH 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.

A method of detecting DNA markers in the 12q22-23 region. The method comprises providing a sample containing acellular DNA from a subject and detecting one or more DNA markers in the 12q22-23 region in the sample. Also disclosed are methods of diagnosing and monitoring cancer; methods of determining the efficacy of a therapy, and the probabilities of survival and responsiveness to a therapy; and packaged products for using these methods.

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.

Detecting cross-contamination between test samples used for determining cancer in a subject is beneficial. To detect cross-contamination, test sequences including at least one single nucleotide polymorphism are prepared using genome sequencing techniques. Some of the test sequences can be filtered to improve accuracy and precision. A prior contamination probability for each test sequence is determined based on a minor allele frequency. A contamination model including a likelihood test is applied to a test sequence. The likelihood test obtains a current contamination probability representing the likelihood that the test sample is contaminated. The contamination model can also determine a likelihood that the sample includes loss of heterozygosity representing the likelihood that the test sequence is contaminated. Test samples that are contaminated are removed. A source for the contaminated test sample can be found by comparing contaminated test sequences to other test sequences.

The invention relates to methods for determining resistance or responsivity to microtubule-targeting drug treatment in cancer patients. The methods comprise obtaining a tumor cell sample from a cancer patient and analyzing DNA in the tumor cell sample to determine the presence or absence of a loss of heterozygosity (LOH) at the M40 β-tubulin gene locus within chromosomal locus 6p25, where determining LOH comprises screening for at least one mutation in the M40 β-tubulin gene that affects the binding of a microtubule-targeting drug to β-tubulin. In such methods, the presence of LOH is indicative of microtubule-targeting drug resistance in the cancer patient or of a decreased likelihood that the cancer patient will respond to therapy with a microtubule-targeting drug.

The invention relates to a method for for detecting mutation and HRD scoring of tumor patient to guide medication, which comprises the following steps: detecting a tumor tissue sample and a control leukocyte sample thereof on the basis of taking a BAM file as an input file, and detecting mutation information of an HRR pathway in panels of different sample types and large-fragment chromosome abnormality HRD caused by gene recombination repair defects, the method for detecting the tumor tissue sample comprises the following steps: 1) detecting mononucleotide mutation of an HRR pathway; 2) detecting the loss of heterozygosity (LOH), telomere allele imbalance (TAI) and large fragment state transition (LST) of the HRR region, wherein the HRD score is equal to the weighted sum of LOH, TAI and LST scores; the invention provides a mutation and HRD scoring medication guidance method for tumor patients. According to the method, a traditional method that the HRD value score is calculated through whole genome detection and is not beneficial to clinical actual effect is optimized, the calculation speed is increased, the detection effect is good, the detection result is accurate, and the requirements of actual application can be well met.

The invention discloses a detection method for detecting 1p/19q combination loss of heterozygosity of chromosome, which comprises the following steps: 1) selecting SNP sites with the same number on 1pand 19q; 2) designing an original primer, modifying a T of each original primer, closest to the 3'end but not at the tail end, into U, if the tail end of the 3'end is T, modifying a second T towardsthe 5'direction into U to obtain a multiplex amplification primer sequence; 3) synthesizing a multiplex amplification primer and dissolving and mixing the multiplex amplification primer; 4) carrying out multiplex PCR amplification; 5) processing the amplification product to enable a single chain of U to form an AP site, and then exposing the 5'phosphoric acid tail end and 3'phosphoric acid tail end of the AP site; 6) sequencing, and judging whether 1p/19q combination loss of heterozygosity occurs on the chromosome according to SNP allelic type frequency. According to the invention, the NGS method based on multiplex amplification is used for detecting Chr1p/19qco-LOH, not only is the detection sensitivity high, and are the specificity and the efficiency high, but also the limitation on samples is small.

A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (i CAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the i CAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

The invention discloses a multiplex PCR (Polymerase Chain Reaction) trapping primer group for a DMD (Duchenne Muscular Dystrophy) gene, a mutation detection kit for the DMD gene and a mutation detection method for the DMD gene. The inventors provide the multiplex PCR trapping primer aiming at the sequences of 79 exons and bilateral 50bp introns and 23 known intron pathogenic mutations of the DMD gene; moreover, the mutation detection method of the DMD gene is provided based on the primer group; the mutation detection method is high in detection sensitivity, good in accuracy, highly consistentin amplification efficiency and low in requirement on quality of a DNA (Deoxyribonucleic Acid) sample, and is used for solving the problem that the complete detection on the mutation information, particularly on loss of heterozygosity/repetition, of the DMD gene is difficultly carried out in one time by adopting a multiplex PCR trapping technique in the prior art.

The invention provides a detection kit to judge whether solid tumors are suited for immunotherapy. The detection kit includes detection reagents for detecting the indexes: tumor mutation load of peripheral blood circulating tumor DNA, HLA typing, HLA state of loss of heterozygosity, PD-L1 membrane expression positive tumor cell percentage, infiltration level of CD8+ immune cells, infiltration level of FOXP3+ immune cells, mRNA expression score of T-cell inflammation related genes, percentage of CD14+CD16-HLA-DR+ monocytes in peripheral blood mononuclear cells, and micro-satellite instability.The invention also provides, correspondingly, a method to judge whether solid tumors are suited for immunotherapy. The kit and method herein can be used to screen patients with solid tumors so as to provide significantly increased objective response rate and have a promising application prospect in terms of clinical screening of patients with solid tumors suited for immunotherapy.

Disclosed is a single stranded primer-promoter-selector construct comprising (in 3′ to 5′ orientation) a primer subsequence annealing to the target, a T7 or other promoter subsequence (the template strand), and a selector subsequence. The primer can be extended by template mediated elongation, including reverse transcription, or ligation to another oligonucleotide. The promoter sequence is oriented to direct the in-vitro transcription (IVT) opposite to that of primer extension, where the selector subsequence serves as a template for IVT. The selector is associated with the target subsequence of interest and it, and the amplified product are unique subsequences, dissimilar to other sequence present in the sample. The construct's is useful for determination of the presence and relative abundance of designated subsequences in the sample, multiplex gene expression analysis, multiplex allele counting, determination of polymorphic/mutation site, and loss of heterozygosity.

The invention relates generally to methods of molecular analysis and particularly to methods of using genetic copy number variations and loss of heterozygosity in the characterization and treatment of disease.

The present invention relates to methods of detection of precancerous lesions and/or cancer. The present invention also relates to the presence of DNA replication stress in precancerous lesions. The present invention further relates to the detection of loss of heterozygosity at common fragile sites and phosphorylated substrates of DNA damage activated kinases.

pp32 is a member of a highly conserved family of differentiation-regulated nuclear proteins that is highly expressed in nearly all human prostatic adenocarcinomas of Gleason Grade≧5. This contrasts with the low percentage of prostate tumors that express molecular alterations in proto-oncogens or demonstrate tumor suppressor mutation or loss of heterozygosity. By analysis of specimens of human prostatic adenocarcinoma and paired adjacent normal prostate from three individual patients, the inventors have shown that normal prostate continues to express normal pp32, whereas three of three sets of RT-PCR-amplified transcripts from prostatic adenocarcinomas display multiple cancer-associated coding sequence changes. The cancer-associated sequence changes appear to be functionally significant. Normal pp32 exerts antineoplastic effects through suppression of transformation. In contrast, cancer-associated pp32 variants augment, rather than inhibit, transformation.

The invention belongs to the field of biotechnology and medicine, relates to oligoden droglioma (OG) markers, and particularly relates to a protein marker MAP2 (microtubuleassociated protein 2) protein which can differentiate OG that clinically has sensitivity to chemotherapy and 1P loss of heterozygosity (1P LOH), and use thereof. According to the invention, the protein marker MAP2 protein which can differentiate the OG that clinically has sensitivity to chemotherapy and 1P loss is determined through the iTRAQ-LC-MS/MS technology. The MAP2 protein has 90% accuracy for the prognosis of the 1P loss. The marker not only can explain the mechanism for the sensitivity to chemotherapy of an OG sample with the 1P LOH, but also can prognose the sensitivity to chemotherapy of an OG patient with the 1P LOH through a decision tree model. The MAP2 protein can be further used for preparing a clinical kit so as to offer help for the diagnosis, the prognosis and the treatment of the OG.

A method of determining a therapeutic regimen in a patient with cancer comprising determining in a sample from the patient the tumor mutation burden (TMB) and loss of heterozygosity (LOH), wherein high TMB in combination with no LOH is indicative of a positive outcome when treated with a checkpoint inhibitor and high TMB with LOH is indicative of a poor outcome, is provided herein.

The invention relates to a simple and convenient method and specific process for detecting SMA. The key point of the technical scheme is that DNA sequencing is carried out on SMN intron 6-exon 8 in the PCR products; if exons 7 and 8 of SMN1 are homozygous deletions, only homozygous peaks of +6T on exon 7 of SMN2 and +245A on exon 8 of SMN2 are found; the method can be used for screening the molecular background of the copy number of the same SMN2 and the phenotypic deviation of the SMA; the +6 position on the exon 7 and +245 position on exon 8 of SMN appear nesting peak; if the phenotype is normal, the subject is normal people; if the subject is a patient, the point mutation of SMN1 can be preliminarily screened. The main application is as follows: the gene level of 98.6 percent of patients can be determined; the molecular background of the same SMN2 copy number and SMA phenotypic deviation can be screened; the remaining few SMA patients with loss of heterozygosity and point mutation are able to screen for point mutations in SMN1. The method is very suitable for basic medical units and is beneficial to further research on the mechanism of the disease.