Molecular profiling and sequential somatic mutation shift in hypermutator tumours harbouring POLE mutations.

ABSTRACT: Defective DNA polymerase ε (POLE) proofreading leads to extensive somatic mutations that exhibit biased mutational properties; however, the characteristics of POLE-mutated tumours remain unclear. In the present study, we describe a molecular profile using whole exome sequencing based on the transition of somatic mutations in 10 POLE-mutated solid tumours that were obtained from 2,042 Japanese patients. The bias of accumulated variations in these mutants was quantified to follow a pattern of somatic mutations, thereby classifying the sequential mutation shift into three periods. During the period prior to occurrence of the aberrant POLE, bare accumulation of mutations in cancer-related genes was observed, whereas PTEN was highly mutated in conjunction with or subsequent to the event, sugges

SUBMITTER: Hatakeyama K 

PROVIDER: S-EPMC5992218 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature