title: A beta-catenin mutation in a sporadic colorectal tumor of the RER phenotype and absence of beta-catenin germline mutations in FAP patients.
abstract: As a signaling protein in the Wnt pathway beta-catenin plays a crucial role in the regulation of cellular proliferation. Recently, oncogenic beta-catenin mutations were described in human colorectal cancer and melanoma cell lines. Since activating mutations in the beta-catenin gene have similar effects on the biochemical level as inactivating mutations in the tumor suppressor gene APC, it is speculated that beta-catenin mutations may substitute APC gene inactivation in carcinogenesis. To address this question we analyzed twenty-three sporadic colorectal tumors of different progression states for mutations in the beta-catenin gene. Eighteen of these tumors showed the wildtype APC gene sequence. In only one of the tumors with wildtype APC a beta-catenin gene mutation was found. This tumor was of the RER (replication error) phenotype which may explain the finding that the mutation occurred in a sequential repeat motif of the beta-catenin gene. The second aim of this study was to investigate whether differences in the phenotypic variability in FAP (familial adenomatous polyposis coli) might be due to inherited alterations in the beta-catenin gene. For this we analyzed DNA from fourteen FAP patients from eight different families for germline mutations in the beta-catenin gene. We did not find any beta-catenin gene alteration in these samples. Our results indicate that somatic beta-catenin activating mutations contribute only to a minor part of human colorectal tumors and that germline beta-catenin mutations do not play a role in the variability of symptoms in FAP.
authors.affiliation: Arbeitsgruppe Tumorgenetik, Abteilung für Strukturelle Biologie, Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Müller
authors.forename: I
authors.initials: I
authors.lastname: Nimmrich
authors.forename: U
authors.initials: U
authors.lastname: Finke
authors.forename: W
authors.initials: W
authors.lastname: Friedl
authors.forename: I
authors.initials: I
authors.lastname: Hoffmann
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000097:blood / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010375:Pedigree; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin