Mathematical Modeling Quantifies "Just-Right" APC Inactivation for Colorectal Cancer Initiation.

ABSTRACT: Dysregulation of the tumor suppressor gene adenomatous polyposis coli (APC) is a canonical step in colorectal cancer development by promoting activation of the WNT/β-catenin pathway. Curiously, most colorectal tumors carry biallelic mutations that result in only partial loss of APC function, suggesting that a "just-right" level of APC inactivation, and hence WNT signaling, provides the optimal conditions for tumorigenesis. Mutational processes act variably across the APC gene, which could contribute to the bias against complete APC inactivation. In this study, we propose a mathematical model to quantify the tumorigenic effect of biallelic APC genotypes, controlling for somatic mutational processes. Analysis of sequence data from >2,500 colorectal cancers showed that APC genotypes resulting

SUBMITTER: Brunet Guasch M 

PROVIDER: S-EPMC7618390 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature