title: beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer.
abstract: Studies of Wnt activation in gastric cancer have yielded conflicting results. The goals of this study were to determine the frequency of Wnt pathway activation and beta-catenin mutation in these tumors. Three hundred eleven gastric cancers were examined for beta-catenin expression by immunostaining and dissected using laser capture microscopy to obtain DNA from those tumors with nuclear beta-catenin. Exon 3 of beta-catenin was amplified using PCR and sequenced. Ninety gastric cancers (29%) displayed nuclear beta-catenin. DNAs from 73 tumors were amplified and sequenced; 19 (26%) contained mutations in exon 3 of beta-catenin, whereas no mutations were detected in 19 tumors negative for beta-catenin nuclear staining (P < 0.05). Most mutations were adjacent to or abolished known regulatory phosphorylation sites. Mutations in exon 3 of beta-catenin are common in gastric cancer that display nuclear beta-catenin. These results suggest that Wnt pathway activation contributes to carcinogenesis in a subset of gastric adenocarcinomas.
authors.affiliation: University of Cincinnati Department of Surgery, Division of Surgical Oncology, Ohio 45219, USA.
authors.forename: Wilson M
authors.initials: WM
authors.lastname: Clements
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.forename: Amod
authors.initials: A
authors.lastname: Sarnaik
authors.forename: On Ja
authors.initials: OJ
authors.lastname: Kim
authors.forename: Jack
authors.initials: J
authors.lastname: MacDonald
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fenoglio-Preiser
authors.forename: Joanna
authors.initials: J
authors.lastname: Groden
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lowy
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013347:Subcellular Fractions / Q000378:metabolism; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin