Generic cancer category multi-gene MSI site targeted detection probe and kit and application

Abstract

The invention relates to a high-coverage generic cancer category multi-gene MSI site targeted detection probe and kit and application. The generic cancer category multi-gene MSI site targeted detection probe comprises at least two of MSI site detection probes with statistical differences in 30 alleles in a tumor and a normal control. Microsatellites are polymorphic DNA loci containing repeated nucleotide sequences, contain a large number of homopolynucleotide sequences, are extremely unbalanced in base distribution, are high in capture difficulty and have high design requirements on the probes. When the generic cancer category multi-gene MSI site targeted detection probe is designed, the difference of the target MSI in the tumor and normal tissues, the coverage degree in capture sequencing and the capture specificity of a target fragment are fully considered. The length of the probe ranges from 80 bp to 120 bp, the longer the probe is, the higher the fault tolerance is, the higher the MSI capture efficiency is, and meanwhile, higher specificity is achieved. Meanwhile, for MSI sites with high repeatability, a head-to-tail type double-probe design is adopted, so that the capture efficiency can be effectively improved.

Description

technical field [0001] The invention relates to the field of tumor detection, in particular to a pan-cancer multigene MSI site-targeted detection probe, kit and application. Background technique [0002] Microsatellites are polymorphic DNA loci containing repetitive nucleotide sequences, usually 2 to 7 nucleotides per unit. Microsatellite instability (MSI) refers to the phenomenon of changes in the length of microsatellite sequences caused by mutations such as insertions or deletions during DNA replication, and is often related to deficient mismatch repair (dMMR). According to the degree of MSI instability, it can be divided into microsatellite sequence high instability (MSI-High, MSI-H), microsatellite sequence low instability (MSI-Low, MSI-L) and microsatellite stability (microsatellite stability, MSS). Tumors with a high incidence of MSI-H include endometrial cancer, colon adenocarcinoma, gastric adenocarcinoma, and rectal adenocarcinoma. [0003] Study finds that MSI ...

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Problems solved by technology

[0004] At present, MSI-PCR and MMR-IHC methods are widely used in clinical practice to detect MSI. However, due to the small number of detection sites or proteins, and the detection results are highly dependent on subjective experience judgments, it is often impossible to accurately predict the MSI status of patients. It is designed for the diagnosis of hereditary mismatch repair deficiency or Lynch syndrome, and it may be biased when used in other cancer types, which will cause a certain degree of false negative results, resulting in some cancer patients losing the opportunity to benefit from immunotherapy

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