Patterns of germline and somatic mutations in 16 genes associated with mismatch repair function or containing tandem repeat sequences
Autor: | Wen Yi Liang, Shung Haur Yang, Pei Ching Lin, Chien Hsing Lin, Wei Shone Chen, Yuan Tzu Lan, Jeng Kai Jiang, Shih Ching Chang, Jen Kou Lin |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Cancer Research congenital hereditary and neonatal diseases and abnormalities Somatic hypermutation colorectal cancer Biology MLH1 medicine.disease_cause lcsh:RC254-282 DNA Mismatch Repair Germline EMAST 03 medical and health sciences 0302 clinical medicine Germline mutation Mutation Rate medicine Biomarkers Tumor Humans Radiology Nuclear Medicine and imaging Prospective Studies MSI Aged Original Research Mutation POLD1 Microsatellite instability Clinical Cancer Research medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Prognosis MMR digestive system diseases MSH6 030104 developmental biology DNA Repair Enzymes Oncology Tandem Repeat Sequences 030220 oncology & carcinogenesis Cancer research Female Colorectal Neoplasms Follow-Up Studies |
Zdroj: | Cancer Medicine Cancer Medicine, Vol 9, Iss 2, Pp 476-486 (2020) |
ISSN: | 2045-7634 |
Popis: | Background We assumed that targeted next‐generation sequencing (NGS) of mismatch repair‐associated genes could improve the detection of driving mutations in colorectal cancers (CRC) with microsatellite instability (MSI) and microsatellite alterations at selected tetranucleotide repeats (EMAST) and clarify the somatic mutation patterns of CRC subtypes. Material and methods DNAs from tumors and white blood cells were obtained from 81 patients with EMAST(+)/MSI‐high (MSI‐H), 78 patients with EMAST(+)/microsatellite stable (MSS), and 72 patients with EMAST(−)/MSI‐H. The germline and somatic mutations were analyzed with a 16‐genes NGS panel. Results In total, 284 germline mutations were identified in 161 patients. The most common mutations were in EPCAM (24.8%), MSH6 (24.2%), MLH1 (21.7%), and AXIN2 (21.7%). Germline mutations of AXIN2, POLE, POLD1, and TGFBR2 also resulted in EMAST and MSI. EMAST(+)/MSI‐H tumors had a significant higher mutation number (205.9 ± 95.2 mut/MB) than tumors that were only EMAST(+) or MSI‐H (118.6 ± 64.2 and 106.2 ± 54.5 mut/MB, respectively; both P For patients with microsatellite instability or microsatellite alterations at selected tetranucleotide repeats, the somatic mutation burden occurs due to the dysfunction of downstream effectors but not the affected gene with germline mutation. The dysfunction of AXIN2 might affect both the canonical APC pathway and the hypermutation mechanism. |
Databáze: | OpenAIRE |
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