Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma

B. R. Seizinger, G. A. Rouleau, L. J. Ozelius, A. H. Lane, G. E. Farmer, J. M. Lamiell, J. Haines, J. W.M. Yuen, D. Collins, D. Majoor-Krakauer, T. Bonner, C. Mathew, A. Rubenstein, John Halperin, A. McConkie-Rosell, J. S. Green, J. A. Trofatter, B. A. Ponder, L. Eierman, M. I. Bowmer & 11 others R. Schimke, B. Oostra, N. Aronin, D. I. Smith, H. Drabkin, M. H. Waziri, W. J. Hobbs, R. L. Martuza, P. M. Conneally, Y. E. Hsia, J. F. Gusella

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)268-269
Number of pages2
JournalNature
Volume332
Issue number6161
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

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von Hippel-Lindau Disease
Chromosomes, Human, Pair 3
Renal Cell Carcinoma
Neoplasms
Chromosomes
Oncogenes
Hemangioblastoma
Pheochromocytoma
Tumor Suppressor Genes
Genes
Cause of Death
Central Nervous System
Phenotype
Kidney
Mutation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Seizinger, B. R., Rouleau, G. A., Ozelius, L. J., Lane, A. H., Farmer, G. E., Lamiell, J. M., ... Gusella, J. F. (1988). Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature, 332(6161), 268-269. https://doi.org/10.1038/332268a0
Seizinger, B. R. ; Rouleau, G. A. ; Ozelius, L. J. ; Lane, A. H. ; Farmer, G. E. ; Lamiell, J. M. ; Haines, J. ; Yuen, J. W.M. ; Collins, D. ; Majoor-Krakauer, D. ; Bonner, T. ; Mathew, C. ; Rubenstein, A. ; Halperin, John ; McConkie-Rosell, A. ; Green, J. S. ; Trofatter, J. A. ; Ponder, B. A. ; Eierman, L. ; Bowmer, M. I. ; Schimke, R. ; Oostra, B. ; Aronin, N. ; Smith, D. I. ; Drabkin, H. ; Waziri, M. H. ; Hobbs, W. J. ; Martuza, R. L. ; Conneally, P. M. ; Hsia, Y. E. ; Gusella, J. F. / Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. In: Nature. 1988 ; Vol. 332, No. 6161. pp. 268-269.
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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.",
author = "Seizinger, {B. R.} and Rouleau, {G. A.} and Ozelius, {L. J.} and Lane, {A. H.} and Farmer, {G. E.} and Lamiell, {J. M.} and J. Haines and Yuen, {J. W.M.} and D. Collins and D. Majoor-Krakauer and T. Bonner and C. Mathew and A. Rubenstein and John Halperin and A. McConkie-Rosell and Green, {J. S.} and Trofatter, {J. A.} and Ponder, {B. A.} and L. Eierman and Bowmer, {M. I.} and R. Schimke and B. Oostra and N. Aronin and Smith, {D. I.} and H. Drabkin and Waziri, {M. H.} and Hobbs, {W. J.} and Martuza, {R. L.} and Conneally, {P. M.} and Hsia, {Y. E.} and Gusella, {J. F.}",
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Seizinger, BR, Rouleau, GA, Ozelius, LJ, Lane, AH, Farmer, GE, Lamiell, JM, Haines, J, Yuen, JWM, Collins, D, Majoor-Krakauer, D, Bonner, T, Mathew, C, Rubenstein, A, Halperin, J, McConkie-Rosell, A, Green, JS, Trofatter, JA, Ponder, BA, Eierman, L, Bowmer, MI, Schimke, R, Oostra, B, Aronin, N, Smith, DI, Drabkin, H, Waziri, MH, Hobbs, WJ, Martuza, RL, Conneally, PM, Hsia, YE & Gusella, JF 1988, 'Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma', Nature, vol. 332, no. 6161, pp. 268-269. https://doi.org/10.1038/332268a0

Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. / Seizinger, B. R.; Rouleau, G. A.; Ozelius, L. J.; Lane, A. H.; Farmer, G. E.; Lamiell, J. M.; Haines, J.; Yuen, J. W.M.; Collins, D.; Majoor-Krakauer, D.; Bonner, T.; Mathew, C.; Rubenstein, A.; Halperin, John; McConkie-Rosell, A.; Green, J. S.; Trofatter, J. A.; Ponder, B. A.; Eierman, L.; Bowmer, M. I.; Schimke, R.; Oostra, B.; Aronin, N.; Smith, D. I.; Drabkin, H.; Waziri, M. H.; Hobbs, W. J.; Martuza, R. L.; Conneally, P. M.; Hsia, Y. E.; Gusella, J. F.

In: Nature, Vol. 332, No. 6161, 01.01.1988, p. 268-269.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma

AU - Seizinger, B. R.

AU - Rouleau, G. A.

AU - Ozelius, L. J.

AU - Lane, A. H.

AU - Farmer, G. E.

AU - Lamiell, J. M.

AU - Haines, J.

AU - Yuen, J. W.M.

AU - Collins, D.

AU - Majoor-Krakauer, D.

AU - Bonner, T.

AU - Mathew, C.

AU - Rubenstein, A.

AU - Halperin, John

AU - McConkie-Rosell, A.

AU - Green, J. S.

AU - Trofatter, J. A.

AU - Ponder, B. A.

AU - Eierman, L.

AU - Bowmer, M. I.

AU - Schimke, R.

AU - Oostra, B.

AU - Aronin, N.

AU - Smith, D. I.

AU - Drabkin, H.

AU - Waziri, M. H.

AU - Hobbs, W. J.

AU - Martuza, R. L.

AU - Conneally, P. M.

AU - Hsia, Y. E.

AU - Gusella, J. F.

PY - 1988/1/1

Y1 - 1988/1/1

N2 - 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.

AB - 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.

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Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM et al. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature. 1988 Jan 1;332(6161):268-269. https://doi.org/10.1038/332268a0