Carcinogenesis in MYH-Associated Polyposis Follows a Distinct Genetic Pathway

摘要: Colorectal carcinomas develop according to particular genetic pathways, including the chromosomal instability (CIN+), microsatellite (MSI+) and MSI- CIN- routes. We have determined pathway in patients with MYH-associated polyposis (MAP), a syndrome of colorectal adenomas cancer that results from defective base excision repair (BER). As previous studies, MAP tumors showed high frequency G>T mutations APC, accordance BER. found K-ras were common tumors, all changes comprising conversion first guanine residue codon 12 thymidine (G12C, GGT>TGT). no BRAF at 599 hotspot or elsewhere exon 14. Almost cancers near-diploid (CIN-), none was MSI+. A few p53 found, but these not predominantly changes. overexpression was, however, frequent. No SMAD4 TGFBIIR found. appear follow distinct pathway, some features both CIN MSI pathways. BER deficiency is rarely accompanied by MSI. The spectrum somatic reflects selection hypermutation which certain residues are particularly prone.