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 tumors as well as to the hereditary tumors that usually accompany familial adenomatous polyposis (FAP). Adenomatous polyposis coli (APC) mutations cause an intracellular accumulation of beta-catenin that results in abnormal signaling in the wnt/wingless pathway. Mutations of the beta-catenin gene itself have also been noted in several types of tumors. In this study we screened the beta-catenin gene in 13 sporadic desmoid tumors for alterations in exon 3, which encodes several serine/threonine residues that are targets for phosphorylation by GSK-3beta. Somatic substitutions at codons 41 (threonine) and 45 (serine) were identified in seven independent tumors, respectively. Although no APC mutations were detected among the remaining six tumors, we found accumulation of beta-catenin by Western blotting analysis in one such tumor for which frozen tissues were available. Our results have suggested that possible involvement of beta-catenin activation by beta-catenin gene mutation or alteration of other factor(s) can contribute to desmoid tumorigenesis.
Miyoshi
Y
Y
Department of Medical Genetics, Osaka University Medical School, Suita-shi, Japan.
Iwao
K
K
Nawa
G
G
Yoshikawa
H
H
Ochi
T
T
Nakamura
Y
Y
D011125:Adenomatous Polyposis Coli; D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000235:genetics*; D018222:Desmoid Tumors / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin