title: Chibby, a novel antagonist of the Wnt pathway, is not involved in Wilms tumor development.
abstract: Deregulation of the Wnt signalling pathway is a key event in the development of a broad spectrum of human malignancies and mutations in beta-catenin (CTNNB1), a central component of the Wnt pathway, have been detected in 10-15% of Wilms tumors (nephroblastoma). Furthermore, nuclear immunoreactivity for beta-catenin has been described even in the absence of detectable beta-catenin mutations. This suggests that other components of the Wnt pathway may be involved in the pathogenesis of a subgroup of Wilms tumors. Chibby (C22ORF2) is a recently identified antagonistic component of the Wnt pathway that inhibits the transcriptional activity of beta-catenin. Our study addresses the question whether mutation or down-regulation of Chibby is involved in Wilms tumorigenesis. We analysed the expression of Chibby by real time RT-PCR in 142 Wilms tumors, but there was no significant expression difference in any group of tumors stratified according to clinical, histological and mutational criteria. Mutation analysis of a smaller cohort did not reveal any mutations of the coding sequence. We only detected a constitutive splice variant leading to the absence of exon 4 in all Wilms tumors as well as in normal tissues. In addition, we detected a frequent silent polymorphism in the Chibby exon 4 sequence (435T/C). These data strongly suggest that despite its attractive function as a modulator of beta-catenin activity, Chibby is not involved in Wilms tumorigenesis.
authors.affiliation: Theodor-Boveri-Institut fuer Biowissenschaften, Physiologische Chemie I, Am Hubland, D-97074 Wuerzburg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Zirn
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wittmann
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Manfred
authors.initials: M
authors.lastname: Gessler
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007680:Kidney Neoplasms / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D009396:Wilms Tumor / Q000235:genetics*; D051153:Wnt Proteins
chemical_list: C473750:CBY1 protein, human; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D051153:Wnt Proteins