Haploinsufficient phenotypes promote selection of PTEN and ARID1A deficient clones in human colon

ABSTRACT: Cancer driver mutations are defined by their high prevalence in cancers and presumed rarity in normal tissues. However, recent studies show that positive selection in normal epithelia can increase the prevalence of some cancer drivers. To determine their true cancer-driving potential, it is essential to evaluate how frequent these mutations are in normal tissues and what their phenotypes are. Here, we explore the bioavailability of somatic variants by quantifying age-related mutational burdens in normal human colonic epithelium using immune detection in FFPE samples (N=181 patients). Positive selection of variants of tumour suppressor genes PTEN and ARID1A associates with monoallelic gene loss as confirmed by CRISPR/Cas9 mutagenesis and changes in their downstream effectors. Comparison of

SUBMITTER: Nefeli Skoufou-Papoutsaki 

PROVIDER: S-SCDT-10_1038-S44319-025-00373-0 | biostudies-other |

REPOSITORIES: biostudies-other