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Method for predicating homologous recombination deficiency mechanism and method for predicating response of patients to cancer therapy

A technology of homologous recombination and mechanism, applied in the field of biological information, can solve the problems of fixed computing type, lack of homologous recombination mechanism, copy number variation, etc.

Inactive Publication Date: 2017-10-24
SHANGHAI ORIGIMED CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In particular, when this type of mutation occurs in genes involved in homologous recombination-related metabolic pathways, the homologous recombination mechanism will be lost, such as TP53 (Tumor Suppressor Gene, tumor suppressor gene), BRCA2 (Breast Cancer Type 2, breast cancer No. 2 gene ), RET (Rearranged During Transfection, proto-oncogene), RB1 (Retinoblastoma Gene, retinoblastoma gene) and other gene copy number variation, and the deletion of PTEN gene, etc.
Therefore, the calculation types of known algorithms are relatively fixed, and cannot predict more types of chromosomal variation for homologous recombination loss
Moreover, with the continuous development and updating of high-throughput sequencing technology, the current research or application of the main technology is next-generation sequencing technology, while the current HRD prediction technology is mainly based on SNP chip technology, and there is a mismatch between the data production platform and the algorithm prediction mechanism For example, the existing technology platforms mostly use SNP chip technology, and the algorithm prediction mainly uses the data values ​​generated by the chip platform instrument itself for direct calculation, but the sequencing technology does not have corresponding data values, requiring new calculation method, so its limitations are relatively large

Method used

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  • Method for predicating homologous recombination deficiency mechanism and method for predicating response of patients to cancer therapy
  • Method for predicating homologous recombination deficiency mechanism and method for predicating response of patients to cancer therapy
  • Method for predicating homologous recombination deficiency mechanism and method for predicating response of patients to cancer therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0174] Example 1 Obtaining the Gene Sequences of Tumor Samples and Normal Samples

[0175] 1. Acquisition of targeted gene bank

[0176] 1.1 Sample processing

[0177] Obtain tumor samples and normal samples from the same patient, perform DNA extraction, and use quantitative instruments (such as Nanodrop instruments) for quantification, so as to determine whether the DNA quality of normal sample DNA and tumor samples meets the subsequent sequencing requirements. The kit is used to extract sample DNA, followed by DNA amplification to obtain sufficient tumor DNA samples and normal DNA samples respectively.

[0178] Wherein, the sample type includes but is not limited to one of FFPE (paraffin-embedded sample), tissue (tissue cut from the patient's body) sample, and blood (blood drawn from the patient's body) sample. According to different sample types, select Different kits are used to extract DNA from normal samples and tumor samples. For example, FFPE samples are extracted wi...

Embodiment 2

[0187] Embodiment 2 Calculation of large fragment INDEL score value

[0188] Calculation of large fragment INDEL score (ie OM-INDEL score): OM-INDEL score is the number of regions where large fragment INDEL (insertion length ≥ 25bp and deletion fragment length ≥ 50bp) occurs.

[0189] The algorithm operation flow is as follows:

[0190] 1. Select high-quality sequencing sequences

[0191] The target gene sequence of the tumor sample obtained in Example 1 and the target gene sequence of the normal sample are respectively subjected to base quality screening, and if a sequencing sequence has one or more base quality values ​​lower than 20, then filter the sequence to obtain the base quality Both tumor sample sequences and normal sample sequences are greater than 20.

[0192] The base quality screening of the present invention is suitable for higher sequencing depths, such as sequences with a sequencing depth greater than 500X-1000X, and can reduce the impact of system sequencin...

Embodiment 3

[0202] Example 3 Calculation of Copy Number Variation Score Values

[0203] The fractional copy number variation value is the number of regions where copy number amplification and copy number loss occurred, ie copy number variation HRD-CNV.

[0204] Using the normal sample comparison result obtained in step 3 of Example 1 and the tumor sample comparison result as input, use copy number variation software to perform CNV (Copy Number Variants, i.e. copy number variation) analysis (for example, EXCAVATOR) to determine the tumor In which regions of the chromosome are amplification and deletion occurred in the sample, the number of amplification and deletion regions is counted, and this number is the HRD-CNV score. When the HRD-CNV score is 0, it means that the sample has no copy number amplification or copy Conversely, when the HRD-CNV score is not 0, it means that the sample has copy number amplification or copy number deletion.

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Abstract

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.

Description

technical field [0001] The invention relates to the field of biological information, in particular to a method for predicting the mechanism of homologous recombination loss and the patient's response to cancer treatment. Background technique [0002] The development of cancer requires a series of lesion stages. Its development process is dominated by gene mutations, including DNA, RNA, protein and other levels of lesions. Among them, DNA changes are an important factor in the occurrence of cancer, including single nucleotide mutations. (Single Nucleotide Polymorphism, SNP), small insertion and deletion (Small INDEL, INDEL is the abbreviation of Insertion / Deletion, the length is usually less than 50bp), large structural variation and other common forms of variation. With the deepening of cancer research, the importance of Homologous Recombination Deficiency (HRD) mechanism in different cancers has been continuously discovered. More than 50% of patients with high-grade serous...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68G06F19/20G06F19/22
CPCC12Q1/6886C12Q2600/106C12Q2600/156G16B25/00G16B30/00
Inventor 陈丽娟王凯秦公炜
Owner SHANGHAI ORIGIMED CO LTD
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