Abstract
Von Hippel–Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas1–3. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Melmon, K. L. & Rosen, S. W. Am. J. Med. 36, 595–617 (1964).
Go, R. C. P., Lamiell, J. M., Hsia, Y. E., Yuen, J. W. M. & Paik, Y. Am. J. hum. Genet. 36, 131–142 (1984).
Huson, S. M. et al. Brain 109, 1297–1310 (1986).
Bonner, T. et al. Science 223, 71–74 (1984).
Yoshida, M. A. et al. Cancer Genet. Cytogenet. 19, 351–354 (1986).
Zbar, B., Brauch, H., Talmadge, C. & Linehan, M. Nature 327, 721–724 (1987).
Bonner, T. I. et al. Nucleic Acids Res. 14, 1009–1015 (1986).
Lathrop, G. M. & Lalouel, J. M. Am. J. hum. Genet. 36, 460–465 (1984).
Hodge, S. E., Morton, L. A., Tideman, S., Kidd, K. K. & Spence, M. A. Am. J. hum. Genet. 31, 761–762 (1979).
Knudson, A. G. Cancer Res. 45, 1437–1443 (1985).
King, C. R. et al Cancer Genet. Cytogenet. 27, 345–348 (1987).
Gusella, J. F. et al. Proc. natn. Acad. Sci. U.S.A. 76, 5239–5243 (1979).
Green, J. S., Bowmer, M. I. & Johnson, G. J. Can. med. Ass. J. 134, 133–138 (1986).
Seizinger, B. R., Martuza, R. L. M. & Gusella, J. F. Nature 322, 644–647 (1986).
Anderson, M. A. & Gusella, J. F. In Vitro 11, 856–858 (1984).
Seizinger, B. R. et al. Cell 49, 589–594 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Seizinger, B., Rouleau, G., Ozelius, L. et al. Von Hippel–Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature 332, 268–269 (1988). https://doi.org/10.1038/332268a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/332268a0
This article is cited by
-
Challenges in Paragangliomas and Pheochromocytomas: from Histology to Molecular Immunohistochemistry
Endocrine Pathology (2021)
-
Genomic profiling in renal cell carcinoma
Nature Reviews Nephrology (2020)
-
Expression of von Hippel–Lindau tumor suppressor protein (pVHL) characteristic of tongue cancer and proliferative lesions in tongue epithelium
BMC Cancer (2017)
-
New diagnosis of von Hippel–Lindau on CT
Internal and Emergency Medicine (2017)
-
Hereditäre Tumorsyndrome in der Neuropathologie
Der Pathologe (2017)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.