Inactivation of germline mutant APC alleles by attenuated somatic mutations: a molecular genetic mechanism for attenuated familial adenomatous polyposis.

ABSTRACT: Germline mutations of the adenomatous polyposis coli (APC) tumor-suppressor gene result in familial adenomatous polyposis (FAP). Patients with FAP typically develop hundreds to thousands of benign colorectal tumors and early-onset colorectal cancer. A subset of germline APC mutations results in an attenuated FAP (AFAP) phenotype, in which patients develop fewer tumors and develop them at an older age. Although a genotype-phenotype correlation between the locations of APC germline mutations and the development of AFAP has been well documented, the mechanism for AFAP has not been well defined. We investigated the mechanism for AFAP in patients carrying a mutant APC allele (APC(AS9)) that has a mutation in the alternatively spliced region of exon 9. APC(AS9) was found to down-regulate beta-ca

SUBMITTER: Su LK 

PROVIDER: S-EPMC1287518 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature