Mutational processes shape the landscape of TP53 mutations in human cancer.

ABSTRACT: Unlike most tumor suppressor genes, the most common genetic alterations in tumor protein p53 (TP53) are missense mutations^1,2. Mutant p53 protein is often abundantly expressed in cancers and specific allelic variants exhibit dominant-negative or gain-of-function activities in experimental models^3-8. To gain a systematic view of p53 function, we interrogated loss-of-function screens conducted in hundreds of human cancer cell lines and performed TP53 saturation mutagenesis screens in an isogenic pair of TP53 wild-type and null cell lines. We found that loss or dominant-negative inhibition of wild-type p53 function reliably enhanced cellular fitness. By integrating these data with the Catalog of Somatic Mutations in Cancer (COSMIC) mutational signatures database^9,10

SUBMITTER: Giacomelli AO 

PROVIDER: S-EPMC6168352 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature