Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light.

ABSTRACT: Mutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here, we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG > TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer contextual patterns improves modeling of UV mut

SUBMITTER: Lindberg M 

PROVIDER: S-EPMC6789905 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature