Carcinogenesis in MYH-Associated Polyposis Follows a Distinct Genetic Pathway

Abstract

Colorectal carcinomas develop according to particular genetic pathways, including the chromosomal instability (CIN+), microsatellite instability (MSI+) and MSI-CIN-routes. We have determined the genetic pathway in patients with MYH-associated polyposis (MAP), a syndrome of colorectal adenomas and cancer that results from defective base excision repair (BER). As in previous studies, MAP tumors showed a high frequency of G > T mutations in APC, in accordance with defective BER. We found that K-ras mutations were common in MAP tumors, all of the changes comprising conversion of the first guanine residue of codon 12 to thymidine (G12C, GGT>TGT). We found no BRAF mutations at the codon 599 hotspo..