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

Yoshikiyo Akasaka, Haruhito Kikuchi, Toshihiro Nagai, Nobuyoshi Hiraoka, Shingo Kato, Jun ichi Hata

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)39-43
Number of pages5
JournalFEBS Letters
Volume317
Issue number1-2
DOIs
Publication statusPublished - 1993 Feb 8

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Denys-Drash Syndrome
Urogenital Abnormalities
Wilms Tumor
Point Mutation
Tumors
Genes
Alleles
Mutation
Zinc Fingers
Polymerase chain reaction
Exons
Polymorphism
Conformations
Zinc
Polymerase Chain Reaction
Amino Acid Substitution
Sequence Analysis
Nucleotides
Screening
Substitution reactions

Keywords

  • Denys-Drash syndrome
  • Point mutation
  • Wilms' tumor
  • WT1 gene

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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. / Akasaka, Yoshikiyo; Kikuchi, Haruhito; Nagai, Toshihiro; Hiraoka, Nobuyoshi; Kato, Shingo; Hata, Jun ichi.

In: FEBS Letters, Vol. 317, No. 1-2, 08.02.1993, p. 39-43.

Research output: Contribution to journalArticle

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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.",
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