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The Wilms tumour gene WT1 is expressed in murine mesoderm–derived tissues and mutated in a human mesothelioma

Nature Genetics volume 4, pages 415–420 (1993)Cite this article

Abstract

The tumour suppressor gene WT1 encodes a transcription factor expressed in tissues of the genito–urinary system. Inactivation of this gene is associated with the development of Wilms tumour a pediatric kidney cancer. We show that WT1 is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. We also describe a case of adult human mesothelioma, a tumour derived from the peritoneal lining, that contains a homozygous point mutation within WT1. This mutation, within the putative transactivation domain, converts the protein from a transcriptional repressor of its target sequence to a transcriptional activator. The role of WT1 in normal development thus extends to diverse structures derived from embryonic mesoderm and disruption of WT1 function contributes to the onset of adult, as well as pediatric, tumours.

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Authors and Affiliations

  1. Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts, 02129, USA

    Seon Park, Amy Bernard, Shyamala Maheswaran, Gwen C. Shipley & Daniel A. Haber

  2. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Martin Schalling & David E. Housman

  3. Department of Pathology, Divisions of Women's and Perinatal Pathology and Solid tumour Cytogenetics, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA

    Drucilla Roberts & Jonathan Fletcher

  4. Department of Research, Kantonsspital, CH4031, Basel, Switzerland

    Robert Shipman

  5. Biosurface Technology Inc., Cambridge, Massachusetts, 02139, USA

    James Rheinwald

  6. Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, 02115, USA

    George Demetri & James Griffin

  7. Princess Margaret Hospital, Toronto, Canada, M4 X 1KG

    Mark Minden

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Park, S., Schalling, M., Bernard, A. et al. The Wilms tumour gene WT1 is expressed in murine mesoderm–derived tissues and mutated in a human mesothelioma. Nat Genet 4, 415–420 (1993). https://doi.org/10.1038/ng0893-415

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