System and method for tumor heterogeneity assessment

Abstract

The invention discloses a system and a method for tumor heterogeneity assessment and particularly provides a molecular clone analysis method. On the basis of various types of variation detection results of high-throughput sequencing in circulating tumor DNA, all variations are divided into different molecular clones to realize tumor heterogeneity assessment by molecular clone levels. By adoption of the method, tumor heterogeneity assessment based on ctDNA high-throughput variation detection is realized to effectively assist in making of tumor prognosis and treatment schemes.

Description

technical field [0001] The invention belongs to the field of biotechnology, and more specifically, the invention relates to methods and systems for assessing tumor heterogeneity. Background technique [0002] Tumor is a disease caused by genetic changes. Tumors often involve a variety of genetic variation types, including single nucleotide variation (Single Nucleotide Variations, SNV), short insertion and deletion (small insertions and deletions, indel), copy number variation (Copy Number Variations, CNV), structural variation (Structure Variations, SV) and so on. The process of accumulation of mutations begins when the first mutation is formed in tumor cells. As time progresses and tumors evolve, the harmful mutations that occur first create favorable maintenance conditions for the mutations that occur later, enabling tumor cells to continuously acquire or enhance abilities such as inhibition of apoptosis, infinite replication, and immune escape. Mutations accumulate muc...

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Problems solved by technology

This method has the following disadvantages: (1) There is bias in clinical sampling of multiple sites, which can only represent the molecular variation characteristics of the selected sites, and cannot represent the complexity of the overall tumor; (2) has certain clinical risks; (3) Some types of metastases are difficult to obtain, such as pleural and peritoneal metastases; (4) Inaccurate, through the heterogeneity analysis method of shared variation, the shared variation is identified as the same level, and the shared variation is not specifically divided, so that Inaccurate analysis results (Gerlinger, M.etal. Intratumor heterogeneity and branched evolution revealed by multiregionsequencing. The New England journal of medicine 366,883-892, doi:10.1056 / NEJMoa1113205(2012); Hao, J.J. and temporal clonal evolution in esophageal squamous cell carcinoma. Naturegenetics, doi:10.1038 / ng.3683(2016))

In addition, there are also methods to evaluate tumor heterogeneity only through the copy number variation results of single-point sampling (Oesper, L., Satas, G. & Raphael, B.J. Quantifying tumorheterogeneity in whole-genome and whole-exome sequencing data. Bioinformatics30, 3532 -3540, doi:10.1093 / bioinformatics / btu651(2014)), in addition to the disadvantage of sampling bias, this method also has the disadvantage of low population coverage, that is, it can only cover part of the cancer or population with a large number of copy number variations

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