Functional characterization of the p53 "mutome".

Phenotypic characterization of mutations in the tumor protein p53 (TP53) gene has so far focused on a handful of relatively frequent "hotspot" mutations, accounting for only ~ 30% of cases. We expanded the scope and quantitatively measured the impact of thousands of distinct TP53 mutations in vitro and in vivo, providing insights into the connections between structure, function, evolutionary conservation and clinical impact.