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.
%0 Journal Article
%1 Zirn.2005b
%A Zirn, B.
%A Wittmann, S.
%A Graf, N.
%A Gessler, M.
%D 2005
%J Cancer Lett
%K Carrier Chain Humans Intercellular Kidney Mutation Neoplasms/*genetics Nuclear Peptides;Proteins/metabolism Polymerase Proteins Proteins/*genetics Reaction Signal Signaling Transduction Tumor/*genetics Wilms Wnt
%N 1
%P 115--120
%T Chibby, a novel antagonist of the Wnt pathway, is not involved in Wilms tumor development
%V 220
%X 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.
@article{Zirn.2005b,
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.},
added-at = {2013-01-29T13:47:26.000+0100},
author = {Zirn, B. and Wittmann, S. and Graf, N. and Gessler, M.},
biburl = {https://www.bibsonomy.org/bibtex/203c2c0af6508dfa372d3e5929a71e2f0/ebch},
interhash = {03ef6b6eefdfa52fa2a7b7c5a0533cbd},
intrahash = {03c2c0af6508dfa372d3e5929a71e2f0},
journal = {Cancer Lett},
keywords = {Carrier Chain Humans Intercellular Kidney Mutation Neoplasms/*genetics Nuclear Peptides;Proteins/metabolism Polymerase Proteins Proteins/*genetics Reaction Signal Signaling Transduction Tumor/*genetics Wilms Wnt},
number = 1,
pages = {115--120},
timestamp = {2013-01-29T13:47:32.000+0100},
title = {Chibby, a novel antagonist of the Wnt pathway, is not involved in Wilms tumor development},
volume = 220,
year = 2005
}