title: Frequent association of beta-catenin and WT1 mutations in Wilms tumors.
abstract: The etiology of Wilms tumor, an embryonic kidney tumor, is genetically heterogeneous. One Wilms tumor gene, WT1, which encodes a zinc finger transcription factor, is mutated in 10-20% of Wilms tumors, but it is still not clear what critical cellular pathway(s) is affected by these mutations. Recently beta-catenin mutations have been reported in 6 of 40 (15%) of Wilms tumors. Beta-catenin is the central effector in the Wnt signal transduction pathway, and deregulation of beta-catenin signaling is critical in the development of a number of malignancies. The observation of beta-catenin mutations in Wilms tumors suggests that abrogation of the Wnt signaling pathway also plays a role in some Wilms tumors. To assess the relationship of WT1 mutations vis-à-vis beta-catenin mutations in Wilms tumor, we analyzed 153 primary tumors, and 21 of 153 (14%) carried beta-catenin mutations. Surprisingly, we observed a highly significant (P = 3.6 x 10(-13)) association between WT1 and beta-catenin mutations; 19 of 20 beta-catenin-mutant tumors had also sustained WT1 mutations. By analogy to the patterns of concordant and discordant gene mutations observed in other tumors, our data suggest that mutation of WT1 and beta-catenin affects two different cellular pathways, both of which are critically altered in at least a subset of Wilms tumors.
authors: Department of Biochemistry and Molecular Biology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: S
authors: S
authors: Maiti
authors: R
authors: R
authors: Alam
authors: C I
authors: CI
authors: Amos
authors: V
authors: V
authors: Huff
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D016162:Genes, Wilms Tumor / Q000235:genetics*; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025721:WT1 Proteins; D051176:beta Catenin