Homozygous inactivation of WTI in a Wilms' tumor associated with the WAGR syndrome

Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two‐hit mechanism. A candidate 11p13 Wilms' tumor gene, WTI , has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome 11 allele encompassing the WTI gene. Analysis of the remaining WTI allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA‐binding zinc finger domain that is essential for the function of the WTI polypeptide as a transcriptional regulator. © 1993 Wiley‐Liss, Inc.