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Medientyp: E-Artikel Titel: Target genes of the WNT/β‐catenin pathway in Wilms tumors Beteiligte: Zirn, Birgit; Samans, Birgit; Wittmann, Stefanie; Pietsch, Thorsten; Leuschner, Ivo; Graf, Norbert; Gessler, Manfred Erschienen: Wiley, 2006 Erschienen in: Genes, Chromosomes and Cancer, 45 (2006) 6, Seite 565-574 Sprache: Englisch DOI: 10.1002/gcc.20319 ISSN: 1045-2257; 1098-2264 Entstehung: Anmerkungen: Beschreibung: <jats:title>Abstract</jats:title><jats:p>The WNT/β‐catenin pathway is involved in numerous human cancers. Mutations of the <jats:italic>CTNNB1</jats:italic> (β‐catenin) gene have also been detected in a subset of pediatric Wilms tumors, but the target genes of the deregulated WNT/β‐catenin pathway in these tumors have yet to be identified. To compare gene expression profiles of Wilms tumors with and without mutations of <jats:italic>CTNNB1</jats:italic>, 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 <jats:italic>CTNNB1</jats:italic> mutations revealed several target genes specifically deregulated in <jats:italic>CTNNB1</jats:italic>‐mutated Wilms tumors. Among these, <jats:italic>PITX2, APCDD1,</jats:italic> and two members of the endothelin axis (<jats:italic>EDN3</jats:italic> and <jats:italic>EDNRA</jats:italic>) are directly activated downstream targets of the WNT/β‐catenin pathway that may enhance proliferation of these tumor cells. In addition, several upstream inhibitors of WNT/β‐catenin signaling like <jats:italic>WIF1</jats:italic> and <jats:italic>PRDC</jats:italic> were also strongly up‐regulated in the <jats:italic>CTNNB1</jats:italic>‐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 <jats:italic>ATX/ENPP2</jats:italic> and <jats:italic>RIS1</jats:italic>, 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 <jats:italic>CTNNB1</jats:italic>‐mutated Wilms tumors corresponded to histologically detectable areas of myomatous cells in these tumors that displayed intense and preferential nuclear β‐catenin antibody staining. This article contains Supplementary Material available at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://www.interscience.wiley.com/jpages/1045-2257/suppmat">http://www.interscience.wiley.com/jpages/1045‐2257/suppmat</jats:ext-link>. © 2006 Wiley‐Liss, Inc.</jats:p>