A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys‐Drash syndrome

Abstract

We have analyzed exon 9 of the WT1 gene of 18 non‐familial/sporadic unilateral Wilms' tumors (WTs) from Japanese patients, by the polymerase chain reaction single‐strand conformation polymorphism (PCR‐SSCP) method. After screening these WTs, a nucleotide alternation, which was present on both alleles, was found in only one case. Furthermore, PCR‐SSCP analysis of the constitutional DNA revealed that this patient carried the mutation on only one allele in the germline. Sequence analysis showed that the tumor carried a point mutation (C‐1180 to T‐1180) in WT1 exon 9 of both alleles, resulting in an Arg‐394 to Trp‐394 amino acid substitution within the third zinc finger domain of the WT1 product. Interestingly, this mutation is identical with the most frequent point mutation associated with the Denys‐Drash syndrome. However, the classical triad of Denys‐Drash syndrome does not apply to this patient. This is in the first report of the point mutation in the zinc finger domain of both WT1 alleles in a sporadic unilateral WT without genitourinary abnormalities, and the mutation suggests that some sporadic WTs carry the Denys‐Drash WT1 mutations.