Frequent mutations in the beta-catenin gene in desmoid tumors from patients without familial adenomatous polyposis

Mutations in the APC gene contribute to development of sporadic desmoid tum ors as well as to the hereditary tumors that usually accompany familial ade nomatous polyposis (FAP). Adenomatous polyposis coli (APC) mutations cause an intracellular accumulation of beta-catenin that results in abnormal sign aling in the wnt/wingless pathway. Mutations of the beta-catenin gene itsel f have also been noted in several types of tumors. In this study we screene d the beta-catenin gene in 13 sporadic desmoid tumors for alterations in ex on 3, which encodes several serine/threonine residues that are targets for phosphorylation by GSK-3 beta. Somatic substitutions at codons 41 (threonin e) and 45 (serine) were identified in seven independent tumors, respectivel y. Although no APC mutations were detected among the remaining six tumors, we found accumulation of beta-catenin by Western blotting analysis in one s uch tumor for which frozen tissues were available. Our results have suggest ed that possible involvement of beta-catenin activation by beta-catenin gen e mutation or alteration of other factor(s) can contribute to desmoid tumor igenesis.