Infrequent mutation of the WT1 gene in 77 Wilms' tumors

Authors

  • Dr. M. Gessler,

    Corresponding author
    1. Institut für Humangenetik der Philipps-Universität, D-35037 Marburg, Germany; Fax: 49-931-888-4150
    • Theodor-Boveri-Institut für Biowissen-schaften, Physiologische Chemie I, Am Hubland, D-97074 Würzburg, Germany
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  • A. König,

    1. Institut für Humangenetik der Philipps-Universität, D-35037 Marburg, Germany; Fax: 49-931-888-4150
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  • K. Arden,

    1. Ludwig Institute for Cancer Research and Department of Medicine, University of California at San Diego, La Jolla, California 92093-0660; Fax: 49-931-888-4150
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  • P. Grundy,

    1. Cross Cancer Institute, Edmonton, Alberta, Canada; Fax: 49-931-888-4150
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  • S. Orkin,

    1. Division of Hematology/Oncology, Children's Hospital, Department of Pediatrics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115; Fax: 49-931-888-4150
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  • S. Sallan,

    1. Division of Pediatric Oncology, Dana Farker Cancer Institute and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; Fax: 49-931-888-4150
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  • C. Peters,

    1. Division of Urology, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Fax: 49-931-888-4150
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  • S. Ruyle,

    1. Division of Urology, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Fax: 49-931-888-4150
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  • J. Mandell,

    1. Division of Urology, Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Fax: 49-931-888-4150
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  • F. Li,

    1. Dana-Farber Cancer Institute, Boston, Massachusetts 02115; Fax: 49-931-888-4150
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  • W. Cavenee,

    1. Ludwig Institute for Cancer Research and Department of Medicine, University of California at San Diego, La Jolla, California 92093-0660; Fax: 49-931-888-4150
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  • G. Bruns

    1. Genetics Division, Children's Hospital and Dept. of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; Fax: 49-931-888-4150
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Abstract

Homozygous deletions in Wilms' tumor DNA have been a key step in the identification and isolation of the WT1 gene. Several additional loci are also postulated to contribute to Wilms' tumor formation. To assess the frequency of WT1 alterations we have analyzed the WT1 locus in a panel of 77 Wilms' tumors. Eight tumors showed evidence for large deletions of several hundred or thousand kilobasepairs of DNA, some of which were also cytogenetically detected. Additional intragenic mutations were detected using more sensitive SSCP analyses to scan all 10 WTl exons. Most of these result in premature stop codons or missense mutations that inactivate the remaining WTl allele. The overall frequency of WTl alterations detected with these methods is less than 15%. While some mutations may not be detectable with the methods employed, our results suggest that direct alterations of the WTl gene are present in only a small fraction of Wilms' tumors. Thus, mutations at other Wilms' tumor loci or disturbance of interactions between these genes likely play an important role in Wilms' tumor development. © 1994 Wiley-Liss, Inc.

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