Unequal prognostic potentials of p53 gain-of-function mutations in human cancers associate with drug-metabolizing activity.

ABSTRACT: Mutation of p53 is the most common genetic change in human cancer, causing complex effects including not only loss of wild-type function but also gain of novel oncogenic functions (GOF). It is increasingly likely that p53-hotspot mutations may confer different types and magnitudes of GOF, but the evidences are mainly supported by cellular and transgenic animal models. Here we combine large-scale cancer genomic data to characterize the prognostic significance of different p53 mutations in human cancers. Unexpectedly, only mutations on the Arg248 and Arg282 positions displayed significant association with shorter patient survival, but such association was not evident for other hotspot GOF mutations. Gene set enrichment analysis on these mutations revealed higher activity of drug-metabolizing

SUBMITTER: Xu J 

PROVIDER: S-EPMC3973211 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature