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[Cancer Research 59, 3880-3882, August 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 3880-3882, August 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Mutational Activation of the ß-Catenin Proto-Oncogene Is a Common Event in the Development of Wilms’ Tumors1

Robert Koesters2, Ruediger Ridder, Annette Kopp-Schneider, David Betts, Volker Adams, Felix Niggli, Jakob Briner and Magnus von Knebel Doeberitz

Department of Surgery, University of Heidelberg, 69120 Heidelberg, Germany [R. K., R. R., M. v. K. D.]; Central Division of Biostatistics, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany [A. K-S.]; Children’s Hospital of Zurich, 8032 Zurich, Switzerland [D. B., F. N.]; Heart Center, University of Leipzig, 04289 Leipzig, Germany [V. A.]; and Institute of Histological and Cytological Diagnostics, 5001 Aarau, Switzerland [J. B.]

Activation of ß-catenin-mediated transcription is the nuclear end point of organ-specific Wnt signaling. In the developing kidney, Wnt-4, a secreted glycoprotein, acts as an autoinducer of the mesenchymal to epithelial transition that underlies normal nephron development. Dysregulation of this epithelial transformation process may lead to Wilms’ tumors (WTs). In this study, we investigated the potential role of the ß-catenin proto-oncogene, a candidate downstream target molecule of Wnt-4 signaling, in the development of WTs. In 6 of 40 tumors (15%), mutation analysis revealed heterozygous missense mutations or small deletions that result in the loss of important regulatory phosphorylation sites within the ß-catenin protein. These findings indicate that activating ß-catenin mutations may play a significant role in the development of WTs and establish a direct link between Wilms’ tumorigenesis and the Wnt signal transduction pathway governing normal kidney development.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.