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Mutations of the VHL tumour suppressor gene in renal carcinoma

Nature Genetics volume 7, pages 85–90 (1994)Cite this article

Abstract

Multiple, bilateral renal carcinomas are a frequent occurrence in von Hippel–Lindau (VHL) disease. To elucidate the aetiological role of the VHL gene in human kidney tumorigenesis, localized and advanced tumours from 110 patients with sporadic renal carcinoma were analysed for VHL mutations and loss of heterozygosity (LOH). VHL mutations were identified in 57% of clear cell renal carcinomas analysed and LOH was observed in 98% of those samples. Moreover, VHL was mutated and lost in a renal tumour from a patient with familial renal carcinoma carrying the constitutional translocation, t(3;8)(p14;q24). The identification of VHL mutations in a majority of localized and advanced sporadic renal carcinomas and in a second form of hereditary renal carcinoma indicates that the VHL gene plays a critical part in the origin of this malignancy.

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Authors and Affiliations

  1. Urologic Oncology Section, Surgery Branch, National Cancer Institute, Bethesda, Maryland, 20892, USA

    J.R. Gnarra, Y. Weng, S. Liu, D.R. Duan, C. Florence, R. Pozzatti, M. M. Walther & W.M. Linehan

  2. Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    K. Tory, L. Schmidt, M.H. Wei, H. Li, F. Chen & F.-M. Duh

  3. Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    F. Latif, M.I. Lerman & B. Zbar

  4. Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, 20892, USA

    I. Lubensky

  5. Department of Urology, New York Hospital, Cornell University Medical Center, New York, New York, 50021, USA

    N.H. Bander

  6. Section of Urology, University of Michigan, Ann Arbor, Michigan, 48109, USA

    H.B. Grossman

  7. Laboratory of Molecular Pathology, Technical University Munich,, Trogerstrasse 32, Munich, 81675, Germany

    H. Brauch

  8. University Clinic of Surgery, Heidelberg, Germany

    S. Pomer

  9. Brady Urological Research Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, 21205, USA

    J.D. Brooks & W.B. Isaacs

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  1. J.R. Gnarra
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  2. K. Tory
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  4. L. Schmidt
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  5. M.H. Wei
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  13. C. Florence
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  14. R. Pozzatti
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  15. M. M. Walther
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  17. H.B. Grossman
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  20. J.D. Brooks
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  23. B. Zbar
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Gnarra, J., Tory, K., Weng, Y. et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet 7, 85–90 (1994). https://doi.org/10.1038/ng0594-85

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