Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers

Abstract

MYH-associated polyposis is a recently described, autosomal recessive condition comprising multiple colorectal adenomas and cancer. This disease is caused by germline mutations in the base excision repair (BER) gene MYH. Genes involved in the BER pathway are thus good candidates for involvement in the pathogenesis of sporadic tumors of the large bowel. We have screened a set of 75 sporadic colorectal cancers for mutations in MYH, MTH1, and OGG1. Allelic loss at MYH was also assessed. Selected samples were screened for mutations and allele loss at APC and mutations in p53, K-ras, and β-catenin. A panel of 35 colorectal cancer cell lines was screened for MYH mRNA and protein expression. One of..