Pan-Cancer Analysis of Mutation Hotspots in Protein Domains.

ABSTRACT: In cancer genomics, recurrence of mutations in independent tumor samples is a strong indicator of functional impact. However, rare functional mutations can escape detection by recurrence analysis owing to lack of statistical power. We enhance statistical power by extending the notion of recurrence of mutations from single genes to gene families that share homologous protein domains. Domain mutation analysis also sharpens the functional interpretation of the impact of mutations, as domains more succinctly embody function than entire genes. By mapping mutations in 22 different tumor types to equivalent positions in multiple sequence alignments of domains, we confirm well-known functional mutation hotspots, identify uncharacterized rare variants in one gene that are equivalent to well-charact

SUBMITTER: Miller ML 

PROVIDER: S-EPMC4982675 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature