Method for predicting ovarian cancer homologous recombination defect based on genome copy number variation biomarker and application

A biomarker and copy number variation technology, applied in the field of biomedicine, to achieve the effects of stable prediction, improved survival rate and good accuracy

Active Publication Date: 2021-11-23
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In conclusion, previous studies have suggested that there may be a correlation between CNVs and patients' HR...

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  • Method for predicting ovarian cancer homologous recombination defect based on genome copy number variation biomarker and application
  • Method for predicting ovarian cancer homologous recombination defect based on genome copy number variation biomarker and application
  • Method for predicting ovarian cancer homologous recombination defect based on genome copy number variation biomarker and application

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Embodiment 1

[0034] Application of a method for predicting homologous recombination deficiency in ovarian cancer based on copy number variation

[0035] The flow process of the present invention research is as Figure 5 As shown, in Example 1, 587 ovarian cancer patients from the TCGA-OV cohort were included in the study, and their clinical characteristics and DNA sequencing data were obtained from https: / / www.cancer.gov / tcga.

[0036] According to HRD-score (HRD score), 587 patients were divided into HRD group (HRD score ≥ 42) and non-HRD group (HRD score < 42), HRD score is loss of heterozygosity (Loss of heterozygosis, LOH), large Unweighted sum of Large-scale state Transition (LST) and Telomeric Allelic Imbalance (TAI).

[0037] GISTIC 2.0 was used to measure CNV profiles at the subchromosomal level of the tumor genome, and the segment files of the TCGA-OV cohort (recording the copy number of each locus in the genome) were used as input to GSITIC 2.0 to quantify the CNV status of chro...

Embodiment 2

[0047] Application of a copy number variation-based biomarker to predict pan-cancer homologous recombination deficiency

[0048] The DNA sequencing results of 10,635 patients with 33 cancer types from the TCGA pan-cancer cohort were analyzed to extend the predictive role of CNV for homologous recombination defects in ovarian cancer to other cancer types.

[0049] Calculate the average HRD score for each tumor to obtain the distribution of homologous recombination deficiency status in different tumors, found ovarian serous cystadenocarcinoma (OV), uterine carcinosarcoma (UCS), lung squamous cell carcinoma (LUSC), sarcoma (SARC) , Patients with esophageal cancer (ESCA). HRD scores were predominantly higher in patients with gastric adenocarcinoma (STAD), bladderurethral carcinoma (BLCA), breast cancer (BRCA), and lung adenocarcinoma (LUAD), whereas patients with thyroid cancer (THCA) and acute myelogenous leukemia (AML) had HRD scores lowest( image 3 A). This is consistent wi...

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Abstract

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.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a method and application for predicting homologous recombination deficiency in ovarian cancer based on biomarkers of genome copy number variation. Background technique [0002] Homologous recombination deficiency (HRD) is a common driver of tumorigenesis, leading to damage during DNA double-strand break repair and consequent genomic instability. Deficiency in homologous recombination is a common feature of many tumors, mainly seen in ovarian cancer. Meanwhile, as a therapeutic target, homologous recombination deficiency plays an important role in chemotherapy, targeted therapy and immunotherapy. Cytotoxic agents such as platinum analogues, topoisomerase I inhibitors, topoisomerase II inhibitors, and the antimetabolite gemcitabine have been shown to be effective against homologous recombination-deficient tumors. In contrast, PARP inhibitors show synthetic lethality when applied to cel...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12Q1/6858C12N15/11
CPCC12Q1/6886C12Q1/6858C12Q2600/156C12Q2537/16C12Q2535/122
Inventor 董忠谊吴德华张萌王剑马思聪白雪谭家乐
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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