title: Genetic alterations involving exon 3 of the beta-catenin gene do not play a role in adenocarcinomas of the esophagus.
abstract: Beta-catenin has been identified as an oncogene. Phosphorylation of sites encoded by exon 3 of the beta-catenin gene facilitates degradation of this protein by the adenomatous polyposis coli (apc) gene product. Mutations in these sites or inactivation of apc lead to stabilization of beta-catenin, which then translocates to the nucleus where it modulates the transcription of genes involved in tumor formation. To explore the role of beta-catenin mutations in adenocarcinomas of the esophagus, we screened for genetic alterations in exon 3 in 69 tumor samples. We detected no mutations in exon 3 by PCR-SSCP analysis nor did we find large interstitial deletions involving exon 3. beta-catenin immunostaining on 54 tumors showed focal nuclear staining in 7 tumors and homogeneous nuclear staining in 3 tumors; in the latter; no mutations in the mutation cluster region of apc were detected. These results show that genetic alterations of exon 3 of the beta-catenin gene do not occur and therefore do not contribute to the pathogenesis of esophageal adenocarcinomas. The abnormal cytoplasmic and nuclear localization of beta-catenin indicates that other mechanisms leading to elevated free beta-catenin in these cancers must be involved.
authors.affiliation: The Rotterdam Esophageal-Tumor Study Group, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: B P
authors.initials: BP
authors.lastname: Wijnhoven
authors.forename: F
authors.initials: F
authors.lastname: Nollet
authors.forename: N J
authors.initials: NJ
authors.lastname: De Both
authors.forename: H W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: W N
authors.initials: WN
authors.lastname: Dinjens
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D051379:Mice; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin