Germline Sequencing of Familial and Sporadic Early-Onset Colorectal Cancer: A Novel Pattern of Genes.

ABSTRACT: The majority of early-onset colorectal cancers (EOCRCs) are not substantiated by germline variants in the main CRC predisposition genes (the "DIGE" panel). To identify potentially novel EOCRC-specific predisposition genes, we analyzed 585 cancer pathway genes in an EOCRC patient cohort (n = 87, diagnosis ≤ 40 years, DIGE-), and compared their variant spectrum to the GnomAD cancer-free database. We identified high-impact variants (HVs) in 15 genes significantly over-represented in EOCRC. Among the 32 unrelated patients with a CRC family history (i.e., with a potentially dominant transmission pattern), 9 presented HVs in ten genes, four of which had a DNA repair function. We subsequently sequenced these 15 genes in a cohort of 82 late-onset CRCs (diagnosis ≥ 50 years, DIGE-) and found varian

SUBMITTER: Vande Perre P 

PROVIDER: S-EPMC12111735 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature