Recurrent promoter mutations in melanoma are defined by an extended context-specific mutational signature.

ABSTRACT: Sequencing of whole tumor genomes holds the promise of revealing functional somatic regulatory mutations, such as those described in the TERT promoter. Recurrent promoter mutations have been identified in many additional genes and appear to be particularly common in melanoma, but convincing functional data such as influence on gene expression has been more elusive. Here, we show that frequently recurring promoter mutations in melanoma occur almost exclusively at cytosines flanked by a distinct sequence signature, TTCCG, with TERT as a notable exception. In active, but not inactive, promoters, mutation frequencies for cytosines at the 5' end of this ETS-like motif were considerably higher than expected based on a UV trinucleotide mutational signature. Additional analyses solidify this patte

SUBMITTER: Fredriksson NJ 

PROVIDER: S-EPMC5443578 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature