Nature Genetics
7, 85 - 90 (1994)
doi:10.1038/ng0594-85
Mutations of the VHL tumour suppressor gene in renal carcinomaJ.R. Gnarra1, K. Tory2, Y. Weng1, L. Schmidt2, M.H. Wei2, H. Li2, F. Latif3, S. Liu1, F. Chen2, F.-M. Duh2, I. Lubensky4, D.R. Duan1, C. Florence1, R. Pozzatti1, M. M. Walther1, N.H. Bander5, H.B. Grossman6, H. Brauch7, S. Pomer8, J.D. Brooks9, W.B. Isaacs9, M.I. Lerman3, B. Zbar3
& W.M. Linehan1, 10
1Urologic Oncology Section, Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
2Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
3Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
4Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA
5Department of Urology, New York Hospital, Cornell University Medical Center, New York, New York 50021, USA
6Section of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA
7Laboratory of Molecular Pathology, Technical University Munich, Trogerstrasse 32, 81675 Munich, Germany
8University Clinic of Surgery, Heidelberg, Germany
9Brady Urological Research Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
10Correspondence should be addressed to W.M.L. 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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