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Volume 68 - 2005 - Fasc.1 - Georges Brohée Prize

Analysis of Wnt-Beta catenin signalling in desmoid tumors

Desmoid tumors are fibromatous lesions occurring both spo- radically and in patients with familial adenomatous polyposis (FAP). Because of the association of these tumors with the heredi- tary colorectal cancer syndrome FAP we set out to define the mol- ecular events driving desmoid tumorigenesis, hypothezising these might be identical to events driving colorectal tumorigenesis. We found that whereas FAP-associated desmoid tumors are caused by germline APC mutations followed by somatic inactivation of the wild-type APC allele, sporadic desmoids are usually characterized by oncogenic mutations in the b-catenin gene, both identical mol- ecular alterations to those found in the vast majority of colorectal cancers. Next we set out to investigate the cellular pathways acti- vated by these mutations, and identified activation of the Wnt sig- naling pathway in desmoid tumors. Wnt signaling modulates expression of developmental genes and cell fate via ss-catenin, and has been implicated in many cancer types. Currently we are inves- tigating tissue-specific downstream effectors of the Wnt pathway that might be responsible for the behaviour of these invasive fibrous tumors. Our findings also point to a role for this pathway in the regulation of normal myofibroblast proliferation and suggest novel treatments in desmoid tumors and other fibrous proliferative disorders. (Acta gastroenterol. belg., 2005, 68, 5-9).