%0 Journal Article %1 Zirn.2006 %A Zirn, B. %A Samans, B. %A Wittmann, S. %A Pietsch, T. %A Leuschner, I. %A Graf, N. %A Gessler, M. %D 2006 %J Genes Chromosomes Cancer %K *Gene *Signal Catenin/*genetics/*metabolism DNA;Complementary/metabolism Expression Gene Humans Immunohistochemistry Models;Biological Mutation Profiling Proteins/*metabolism Regulation;Neoplastic Transduction/genetics Tumor/*genetics/metabolism Wilms Wnt beta %N 6 %P 565--574 %T Target genes of the WNT/beta-catenin pathway in Wilms tumors %V 45 %X The WNT/beta-catenin pathway is involved in numerous human cancers. Mutations of the CTNNB1 (beta-catenin) gene have also been detected in a subset of pediatric Wilms tumors, but the target genes of the deregulated WNT/beta-catenin pathway in these tumors have yet to be identified. To compare gene expression profiles of Wilms tumors with and without mutations of CTNNB1, we used 11.5-k cDNA microarrays. Most of the tumors (86\%) had received preoperative chemotherapy as mandated by the European SIOP protocol. The comparison between Wilms tumors with and without CTNNB1 mutations revealed several target genes specifically deregulated in CTNNB1-mutated Wilms tumors. Among these, PITX2, APCDD1, and two members of the endothelin axis (EDN3 and EDNRA) are directly activated downstream targets of the WNT/beta-catenin pathway that may enhance proliferation of these tumor cells. In addition, several upstream inhibitors of WNT/beta-catenin signaling like WIF1 and PRDC were also strongly up-regulated in the CTNNB1-mutated Wilms tumors. This overexpression may be a negative feedback mechanism in tumors with uncontrolled WNT signaling. Moreover, we identified deregulated genes in both the retinoic acid and the RAS pathways, such as ATX/ENPP2 and RIS1, suggesting an association between these two pathways with that of WNT. In addition, the strong representation of muscle-related genes in the expression profile of CTNNB1-mutated Wilms tumors corresponded to histologically detectable areas of myomatous cells in these tumors that displayed intense and preferential nuclear beta-catenin antibody staining. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

@article{Zirn.2006, abstract = {The WNT/beta-catenin pathway is involved in numerous human cancers. Mutations of the CTNNB1 (beta-catenin) gene have also been detected in a subset of pediatric Wilms tumors, but the target genes of the deregulated WNT/beta-catenin pathway in these tumors have yet to be identified. To compare gene expression profiles of Wilms tumors with and without mutations of CTNNB1, we used 11.5-k cDNA microarrays. Most of the tumors (86{\%}) had received preoperative chemotherapy as mandated by the European SIOP protocol. The comparison between Wilms tumors with and without CTNNB1 mutations revealed several target genes specifically deregulated in CTNNB1-mutated Wilms tumors. Among these, PITX2, APCDD1, and two members of the endothelin axis (EDN3 and EDNRA) are directly activated downstream targets of the WNT/beta-catenin pathway that may enhance proliferation of these tumor cells. In addition, several upstream inhibitors of WNT/beta-catenin signaling like WIF1 and PRDC were also strongly up-regulated in the CTNNB1-mutated Wilms tumors. This overexpression may be a negative feedback mechanism in tumors with uncontrolled WNT signaling. Moreover, we identified deregulated genes in both the retinoic acid and the RAS pathways, such as ATX/ENPP2 and RIS1, suggesting an association between these two pathways with that of WNT. In addition, the strong representation of muscle-related genes in the expression profile of CTNNB1-mutated Wilms tumors corresponded to histologically detectable areas of myomatous cells in these tumors that displayed intense and preferential nuclear beta-catenin antibody staining. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.}, added-at = {2013-01-29T13:47:26.000+0100}, author = {Zirn, B. and Samans, B. and Wittmann, S. and Pietsch, T. and Leuschner, I. and Graf, N. and Gessler, M.}, biburl = {https://www.bibsonomy.org/bibtex/235bb7887eec4bfbb3b1ea47839cdc2d7/ebch}, interhash = {865e03181a970f938fd1773fa02220d3}, intrahash = {35bb7887eec4bfbb3b1ea47839cdc2d7}, journal = {Genes Chromosomes Cancer}, keywords = {*Gene *Signal Catenin/*genetics/*metabolism DNA;Complementary/metabolism Expression Gene Humans Immunohistochemistry Models;Biological Mutation Profiling Proteins/*metabolism Regulation;Neoplastic Transduction/genetics Tumor/*genetics/metabolism Wilms Wnt beta}, number = 6, pages = {565--574}, timestamp = {2013-01-29T13:47:32.000+0100}, title = {Target genes of the WNT/beta-catenin pathway in Wilms tumors}, volume = 45, year = 2006 }