A full-proteome, interaction-specific characterization of mutational hotspots across human cancers.

ABSTRACT: Rapid accumulation of cancer genomic data has led to the identification of an increasing number of mutational hotspots with uncharacterized significance. Here we present a biologically informed computational framework that characterizes the functional relevance of all 1107 published mutational hotspots identified in approximately 25,000 tumor samples across 41 cancer types in the context of a human 3D interactome network, in which the interface of each interaction is mapped at residue resolution. Hotspots reside in network hub proteins and are enriched on protein interaction interfaces, suggesting that alteration of specific protein-protein interactions is critical for the oncogenicity of many hotspot mutations. Our framework enables, for the first time, systematic identification of specif

SUBMITTER: Chen S 

PROVIDER: S-EPMC8744679 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature