Patterns of germline and somatic mutations in 16 genes associated with mismatch repair function or containing tandem repeat sequences

Abstract 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