Homozygous somatic Wt1 point mutations in sporadic unilateral Wilms tumor.

AUTOR(ES)

Coppes, M J

RESUMO

Wilms tumor may be caused by loss of function of genes at different loci. A Wilms tumor suppressor gene, WT1, at chromosome 11 band p13, has recently been cloned and characterized. WT1 has been implicated in the development of Wilms tumor by virtue of mutations in patients with genitourinary anomalies and susceptibility to Wilms tumor. Homozygous intragenic mutations have been reported in Wilms tumors, but usually not in sporadic unilateral Wilms tumors, which constitute the majority of Wilms tumor cases. Using the single-strand conformational polymorphism assay, we have identified three sporadic unilateral Wilms tumors with homozygous point mutations: one with a de novo germ-line nonsense point mutation within WT1 exon 8, and two carrying a somatic mutation within WT1 exon 10. In all three cases loss of the wild-type allele was demonstrated by tumor loss of heterozygosity. This report provides an example of two somatic mutations in the same tumor expected to inactivate WT1 function.

Documentos Relacionados

• Zinc finger point mutations within the WT1 gene in Wilms tumor patients.
• Fine structure analysis of the WT1 gene in sporadic Wilms tumors.
• Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression
• Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer
• BASP1 Is a Transcriptional Cosuppressor for the Wilms' Tumor Suppressor Protein WT1