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

FEBS Letters

Nagai, Toshihiro¹  Hata, Jun-ichi¹  Akasaka, Yoshikiyo¹  Hiraoka, Nobuyoshi¹  Kato, Shingo²  Kikuchi, Haruhito¹ 

[1] Department of Pathology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160, Japan;Microbiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160, Japan

关键词: Wilms' tumor;    WT1 gene;    Denys-Drash syndrome;    Point mutation;   

DOI  :  10.1016/0014-5793(93)81487-K

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown