FAMILIAL ADENOMATOUS POLYPOSIS - FROM BEDSIDE TO BENCHSIDE

Familial adenomatous polyposis (FAP) is a dominantly inherited cancer- predisposition syndrome with an incidence of between 1:17,000 and 1:5, 000. The condition has been causally linked to mutation of the adenoma tous polyposis coli (APC) gene located at 5q21. Virtually all mutation s in the APC gene are truncating mutations, resulting in loss of funct ion of the APC protein. Spontaneous germline mutation of this gene occ urs frequently and accounts for the high incidence of FAP. The gene is somatically mutated at an early point in the colorectal adenoma-carci noma progression. Somatic mutations of the APC gene are also frequentl y observed in a variety of other human carcinomas. Isolation of the AP C gene has led to the recognition of genotype-phenotype correlations a nd, together with protein studies, has helped to elucidate the structu re and function of the APC protein. This report aims to take the reade r from a clinical appreciation to a molecular understanding of FAP.