Mutational burden and signatures in 4000 Japanese cancers provide insights into tumorigenesis and response to therapy.

ABSTRACT: Tumor mutational burden (TMB) and mutational signatures reflect the process of mutation accumulation in cancer. However, the significance of these emerging characteristics remains unclear. In the present study, we used whole-exome sequencing to analyze the TMB and mutational signature in solid tumors of 4046 Japanese patients. Eight predominant signatures-microsatellite instability, smoking, POLE, APOBEC, UV, mismatch repair, double-strand break repair, and Signature 16-were observed in tumors with TMB higher than 1.0 mutation/Mb, whereas POLE and UV signatures only showed moderate correlation with TMB, suggesting the extensive accumulation of mutations due to defective POLE and UV exposure. The contribution ratio of Signature 16, which is associated with hepatocellular carcinoma in drinke

SUBMITTER: Hatakeyama K 

PROVIDER: S-EPMC6676127 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature