Genome recombination fingerprint for characterizing hHRD homologous recombination deficiency and identification method thereof

A technology of homologous recombination and genomics, applied in the fields of genomics, microbial measurement/inspection, biochemical equipment and methods, etc., can solve problems such as undiscovered identification methods

Pending Publication Date: 2019-09-17
成都吉诺迈尔生物科技有限公司 +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

No identification method has been found to characterize these disea

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  • Genome recombination fingerprint for characterizing hHRD homologous recombination deficiency and identification method thereof
  • Genome recombination fingerprint for characterizing hHRD homologous recombination deficiency and identification method thereof
  • Genome recombination fingerprint for characterizing hHRD homologous recombination deficiency and identification method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0048] Example 1 High-frequency site-specific copy number variation in the HBV-related liver cancer genome is a characteristic of hHRD fingerprint Method: Surgical sampling of fresh liver cancer and blood tissue, sampling volume> 1cm 3 , the blood sample was 5 ml of anticoagulated blood, and the blood cells were collected by centrifugation. The samples were quickly frozen in liquid nitrogen and placed in individual sealed packages to prevent contamination between samples, and the packaging containers were marked with basic clinical information. The samples were stored at -80°C and shipped to the sequencing company within two weeks on dry ice for sample quality inspection, nucleic acid extraction and sequencing. After genome purification, use Qubit, 1% AGE to detect the degradation of the sample, the concentration is ≥20ng / ul, the total amount is ≥500ng, the sample has no obvious degradation band and can be used for downstream analysis and sequencing.

[0049] The sequencing p...

Embodiment 2

[0056] Example 2 A high proportion of interchromosomal translocation events in HBV-related liver cancer genomes is one of the molecular fingerprints of hHRD

[0057] Methods: Further, the delly software was used to define and count the genome-wide recombination events of HBV-related liver cancer genomes. The software is based on the soft-clipped principle. When deletions, translocations, insertions and other structural variations in the genome cause reads across the deletion site to be compared to the genome, a reads is cut into two segments and matched to different regions (soft-clipped reads) to identify the chromosome structure Variation and integration of foreign sequences. Events with at least three soft-clipped reads covering the breakpoint and one soft-clipped read covering the end of the adapter sequence were screened. SV mutation detection is performed on cancer paired samples (Tumor-Normal), and the SV system mutation data of the tumor itself is obtained.

[0058]...

Embodiment 3

[0059] Example 3 Genome recombination characteristics of HBV-negative liver cancer

[0060] Methods: 4 cases of HBV-negative fresh liver cancer and corresponding individual blood tissues were sampled in the same operation as above, and the whole genome was performed using the illumina2000 sequencer based on the illumina sequencing platform and the Hiseq X-ten paired-end (paired-End) bridge sequencing method Resequencing; delly software was used to analyze the genome recombination characteristics of tumors, and Controlfreec software was used to analyze CNV events.

[0061] Results: A.delly software analysis found that four cases of HBV-negative liver cancer had a low number of genomic structural variations and lacked a high proportion of interchromosomal translocations. The abscissa indicates the sample number, and the ordinate indicates the quantity and composition ratio of the structural variation of each sample. B. Controlfreec software analysis found that four cases of HBV...

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Abstract

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.

Description

[0001] 1. Technical field [0002] The present invention generally relates to a genome recombination fingerprint and bioinformatics identification method for identifying a special homologous recombination repair defect, which is used to identify virus infection, tumor or intermediate pathological state (such as liver cirrhosis, etc.) with this feature. In particular, the invention relates to methods for identifying cells, body fluids or biopsies that are characterized by hHRD-type genomic recombinations. More specifically, the present invention relates to the identification of characteristic genome recombination fingerprints associated with hHRD homologous recombination defects due to hepatitis B infection virus infection or cellular genome mutations, including the total frequency of genome-wide recombination, the composition of chromosomal structural variation types and high-frequency site-specific copy number variation, which can be used to identify diseases related to homolog...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883C12Q1/6886G16B20/50G16B20/20
CPCC12Q1/6883C12Q1/6886G16B20/50G16B20/20C12Q2600/156C12Q2600/106
Inventor 刘聪唐子执姜长安张臣良曾鸣王小军李友伟
Owner 成都吉诺迈尔生物科技有限公司
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