Mutations of the VHL tumour suppressor gene in renal carcinoma

Gnarra, J.R.; Tory, K.; Weng, Y.; Schmidt, L.; Wei, M.H.; Li, H.; Latif, F.; Liu, S.; Chen, F.; Duh, F.-M.; Lubensky, I.; Duan, D.R.; Florence, C.; Pozzatti, R.; Walther, M. M.; Bander, N.H.; Grossman, H.B.; Brauch, H.; Pomer, S.; Brooks, J.D.; Isaacs, W.B.; Lerman, M.I.; Zbar, B.; Linehan, W.M.

doi:10.1038/ng0594-85

Cited by 1,730Renal cell carcinoma treatmentEar and Head TumorsCancer, Hypoxia, and Metabolism

Mutations of the VHL tumour suppressor gene in renal carcinoma

Gnarra, J.R., Tory, K., Weng, Y., Schmidt, L., Wei, M.H., Li, H., Latif, F., Liu, S. +16 more·1994·Nature Genetics

DOI 10.1038/ng0594-85

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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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In ccRCC, VHL loss impairs degradation of HIF-α proteins, leading to HIF accumulation irrespective of oxygen levels.
“In ccRCC, VHL loss impairs degradation of HIF-α proteins, leading to HIF accumulation irrespective of oxygen levels (Gnarra et al., 1994;Krieg et al., 2000).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Gnarra et al., 1994
Most sporadic ccRCCs lose VHL function through genomic alterations.
“In addition, most sporadic ccRCCs lose VHL function through genomic alterations”
From Hypoxic control of metastasis (2016) · cites this paper as [25]

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Authors: Gnarra, J. R., Tory, K., Weng, Y., Schmidt, L., Wei, M. H., Li, H., Latif, F., Liu, S., Chen, F., Duh, F.-M., Lubensky, I., Duan, D. R., Florence, C., Pozzatti, R., Walther, M. M., Bander, N. H., Grossman, H. B., Brauch, H., Pomer, S., Brooks, J. D., Isaacs, W. B., Lerman, M. I., Zbar, B., & Linehan, W. M.
Affiliations: National Cancer Institute (US)
Frederick National Laboratory for Cancer Research (US)
National Institutes of Health (US)
Cornell University (US)
University of Michigan (US)
Technical University of Munich (DE)
Heidelberg University (DE)
Johns Hopkins University (US)
ORCID: Gnarra, J.R.
Schmidt, L.
Wei, M.H.
Lubensky, I.
Bander, N.H.
Brauch, H.
Brooks, J.D.
Isaacs, W.B.
Lerman, M.I.
Linehan, W.M.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1994-05
Volume: 7
Issue: 1
Pages: 85-90
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng0594-85
OpenAlex: W2010160635
Cited by: 1,730
References: 29
Citations by year: 2026: 17 · 2025: 25 · 2024: 30 · 2023: 38 · 2022: 38 · 2021: 45 · 2020: 56 · 2019: 47 · 2018: 45 · 2017: 42 · 2016: 57 · 2015: 35 · 2014: 70 · 2013: 66 · 2012: 62
FWCI: 61.77
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
Health Sciences › Medicine › Oncology › Ear and Head Tumors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords: VHL gene, von Hippel-Lindau disease, renal carcinoma, clear cell renal cell carcinoma, loss of heterozygosity
MeSH terms: Base Sequence, Carcinoma, DNA Mutational Analysis, DNA, Neoplasm, von Hippel-Lindau Disease, Humans, Kidney Neoplasms, Molecular Sequence Data, Mutation, Organ Specificity, Polymorphism, Restriction Fragment Length, Genes, Tumor Suppressor, Neoplasms, Second Primary, Sequence Deletion, Adenocarcinoma, Clear Cell

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Mutations of the VHL tumour suppressor gene in renal carcinoma

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