Mutational activation of the beta-catenin proto-oncogene is a common eventin the development of Wilms' tumors

Activation of beta-catenin-mediated transcription is the nuclear end point of organ-specific Wnt signaling. In the developing kidney, Wnt-4, a secrete d glycoprotein, acts as an autoinducer of the mesenchymal to epithelial tra nsition that underlies normal nephron development. Dysregulation of this ep ithelial transformation process may lead to Wilms' turners (WTs). In this s tudy, we investigated the potential role of the beta-catenin proto-oncogene , a candidate downstream target molecule of Wnt-4 signaling, in the develop ment of WTs. In 6 of 40 tumors (15%), mutation analysis revealed heterozygo us missense mutations or small deletions that result in the loss of importa nt regulatory phosphorylation sites within the beta-catenin protein, These findings indicate that activating beta-catenin mutations may play a signifi cant role in the development of WTs and establish a direct link between Wil ms' tumorigenesis and the Wnt signal transduction pathway governing normal kidney development.