Editor-in-Chief & Deputy Editor 2019-2021





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Georges Brohee Prize

Analysis of Wnt/Beta catenin signalling in desmoid tumors

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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- nalling pathway in desmoid tumors.Wnt signaling modulates expression of developmental genes and cell fate via -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. [Product Details...]