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WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour

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Abstract

WILMS' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1,2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized3,4: it is expressed at high levels in the glomeruli of the kidney5, as well as the gonadal ridge of the developing gonad5, the Sertoli cells of the testis6 and the epithelial and granulosa cells of the ovary6, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development.

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Authors and Affiliations

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

    Jerry Pelletier, Wendy Bruening, Daniel A. Haber, Tom Glaser & David E. Housman

  2. McGill Cancer Center, McGill University, Room 701, 3655 Drummond Street, Montreal, Québec, H3G 1Y6, Canada

    Jerry Pelletier

  3. Clinical Epidemiology Branch, Division of Cancer Etiology, NCI, NIH, Bethesda, Maryland, 20892

    Frederick P. Li

  4. Division of Biostatistics and Epidemiology, Dana-Farber Cancer Institute, Boston, Massachusetts, 02115, USA

    Frederick P. Li

  5. Massachusetts General Hospital Cancer Center, Boston, Massachusetts, 02114, USA

    Daniel A. Haber

  6. Howard Hughes Medical Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Tom Glaser

Authors
  1. Jerry Pelletier
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  2. Wendy Bruening
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  3. Frederick P. Li
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  4. Daniel A. Haber
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  5. Tom Glaser
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  6. David E. Housman
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Pelletier, J., Bruening, W., Li, F. et al. WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour. Nature 353, 431–434 (1991). https://doi.org/10.1038/353431a0

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  • DOI: https://doi.org/10.1038/353431a0

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