Mutational Biases Drive Elevated Rates of Substitution at Regulatory Sites across Cancer Types.

ABSTRACT: Disruption of gene regulation is known to play major roles in carcinogenesis and tumour progression. Here, we comprehensively characterize the mutational profiles of diverse transcription factor binding sites (TFBSs) across 1,574 completely sequenced cancer genomes encompassing 11 tumour types. We assess the relative rates and impact of the mutational burden at the binding sites of 81 transcription factors (TFs), by comparing the abundance and patterns of single base substitutions within putatively functional binding sites to control sites with matched sequence composition. There is a strong (1.43-fold) and significant excess of mutations at functional binding sites across TFs, and the mutations that accumulate in cancers are typically more disruptive than variants tolerated in extant huma

SUBMITTER: Kaiser VB 

PROVIDER: S-EPMC4973979 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature