This study investigated the risk of desmoids in FAP, the relation between specific APC gene mutations and desmoid formation, and the clinical characteristics of FAP patients with desmoids.
FAP is caused by mutations in the APC gene and various genotype-phenotype relationships have been defined including reports that colorectal polyposis is less severe with mutations 5' to codon 157 and that the risk of desmoid tumours is high in FAP patients with APC gene mutations between codons 1444 and 1598.
These findings are compatible with the presence of a "second hit" inactivation of the APC gene and implicate this gene in the pathogenesis of desmoid tumors.
These findings demonstrate (i) that FAP and FIF are allelic, and (ii) that APC gene mutations which truncate the APC protein distal to the beta-catenin binding domain are associated with desmoid tumours, absent CHRPE and variable but attenuated polyposis expression.
A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis.
Mutations in the APC gene contribute to development of sporadic desmoid tumors as well as to the hereditary tumors that usually accompany familial adenomatous polyposis (FAP).