Mouse model and human patient data reveal critical roles for Pten and p53 in suppressing POLE mutant tumor development.

ABSTRACT: Mutations in the exonuclease domain of POLE are associated with tumors harboring very high mutation burdens. The mechanisms linking this significant mutation accumulation and tumor development remain poorly understood. Pole ^+/P286R;Trp53 ^+/- mice showed accelerated cancer mortality compared to Pole ^+/P286R;Trp53 ^+/+ mice. Cells from Pole ^+/P286R mice showed increased p53 activation, and subsequent loss of p53 permitted rapid growth, implicating canonical p53 loss of heterozygosity in POLE mutant tumor growth. However, p53 status had no effect on tumor mutation burden or single base substitution signatures in POLE mutant tumors from mice or humans. Pten has important roles in maintaining

SUBMITTER: Park VS 

PROVIDER: S-EPMC8892059 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature