A germline mutation at the extreme 3′ end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta‐catenin in the desmoid tumor

摘要: Desmoid tumors arise sporadically or as part of the extraintestinal manifestations familial adenomatous polyposis (FAP). In FAP, two distinct clinical presentations desmoid phenotype are seen: 1) one a few present predominantly in abdominal wall abdomen; 2) florid proliferation early life, mostly near axial skeleton extremities. These different phenotypes have been associated with sites germline mutations coli gene (APC gene). We large, French-Canadian kindred tumor caused by mutation at codon 2643-2644 APC gene. The was characterized onset multiple tumors, arising and proximal penetrance 100% this kindred. However, expression disease variable amongst affected relatives. Many carriers had cutaneous cysts. Polyposis colon rarely observed individuals we did not document upper gastro-intestinal polyps. mutant allele express stable truncated protein vivo. Molecular analysis proband's DNA revealed somatic inactivating wild-type allele. Immunohistochemistry on also demonstrated elevated levels beta-catenin. study demonstrates that extreme 3' is severely penetrant attenuated coli. It suggests involvement beta-catenin pathway development FAP. natural history between individuals, surgical interventions to be timed appropriately due frequent recurrences.