Polyclonal origins of human premalignant colorectal lesions.

ABSTRACT: Cancer is generally thought to be caused by expansion of a single mutant cell¹. However, analyses of early colorectal cancer lesions suggest that tumors may instead originate from multiple, genetically distinct cell populations^2,3. Detecting polyclonal tumor initiation is challenging in patients, as it requires profiling early-stage lesions before clonal sweeps obscure diversity. To investigate this, we analyzed normal colorectal mucosa, benign and dysplastic premalignant polyps, and malignant adenocarcinomas (123 samples) from six individuals with familial adenomatous polyposis (FAP). Individuals with FAP have a germline heterozygous APC mutation, predisposing them to colorectal cancer and numerous premalignant polyps by early adulthood⁴. Whole-geno

SUBMITTER: Van Egeren D 

PROVIDER: S-EPMC12642608 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature