| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Urology [T. S., K. K., T. K., Y. K., M. H., M. Y.], Radiology [S. T.], and 2nd Pathology [Y. N.], Yokohama City University School of Medicine, and Department of Clinical Pathology, Yokohama City University Hospital [H. K.], 3-9 Fukuura Kanazawa-ku, Yokohama 236, Japan, and Laboratory of Immunobiology National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [T. K., F. L., B. Z., M. I. L.]
We analyzed 47 primary sporadic human renal cell carcinomas (39 clear cell and 8 non-clear cell) for mutations of the von Hippel-Lindau (VHL) tumor suppressor gene using the polymerase chain reaction and single strand conformational polymorphism analysis of DNA. All of the positive cases in single strand conformational polymorphism analyses were further characterized by direct sequencing. Somatic mutations were detected in 22 (56%) of 39 clear cell renal carcinomas including 15 deletions, 3 insertions, 3 missense mutations, and 1 nonsense mutation. Nineteen of these mutations predicted to produce truncation of the VHL protein. These mutations mainly occurred in the last one-third region of exons 1, 2, and 3. In addition, loss of heterozygosity of the VHL gene was observed in 16 (84%) of 19 informative clear cell renal carcinomas. No somatic mutations were detected in 8 non-clear cell carcinomas. These results show that the VHL tumor suppressor gene is one of the major tumor suppressor genes in human renal cell carcinomas, especially in the clear cell subtype renal cell carcinoma. Clear cell carcinoma might be distinguished from other pathological types of renal cell carcinomas by molecular genetic techniques.
1 This work was supported by a Grant-in-Aid from the Ministry of Education, Science, and Culture, Japan.
2 To whom requests for reprints should be addressed.
Received 2/28/94. Accepted 4/21/94.
This article has been cited by other articles:
|
|
 |
|
  B. I. Rini, S. Halabi, J. E. Rosenberg, W. M. Stadler, D. A. Vaena, S.-S. Ou, L. Archer, J. N. Atkins, J. Picus, P. Czaykowski, et al. Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206 J. Clin. Oncol., November 20, 2008; 26(33): 5422 - 5428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Peters, B. Vaske, K. Albrecht, M. A. Kuczyk, U. Jonas, and J. Serth Adiposity and Age are Statistically Related to Enhanced RASSF1A Tumor Suppressor Gene Promoter Methylation in Normal Autopsy Kidney Tissue Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2526 - 2532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Ryan, B. H. Goldman, P. N. Lara Jr, P. C. Mack, T. M. Beer, C. M. Tangen, D. Lemmon, C.-X. Pan, H. A. Drabkin, and E. D. Crawford Sorafenib With Interferon Alfa-2b As First-Line Treatment of Advanced Renal Carcinoma: A Phase II Study of the Southwest Oncology Group J. Clin. Oncol., August 1, 2007; 25(22): 3296 - 3301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Inoue, N. Nonomura, Y. Kojima, M. Shiba, D. Oka, Y. Arai, M. Nakayama, H. Takayama, K. Nishimura, H. Mori, et al. Somatic mutations of the von Hippel-Lindau disease gene in renal carcinomas occurring in patients with long-term dialysis Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2052 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M. Linehan, P. A. Pinto, R. Srinivasan, M. Merino, P. Choyke, L. Choyke, J. Coleman, J. Toro, G. Glenn, C. Vocke, et al. Identification of the Genes for Kidney Cancer: Opportunity for Disease-Specific Targeted Therapeutics Clin. Cancer Res., January 15, 2007; 13(2): 671s - 679s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Rini and W.K. Rathmell Biological Aspects and Binding Strategies of Vascular Endothelial Growth Factor in Renal Cell Carcinoma Clin. Cancer Res., January 15, 2007; 13(2): 741s - 746s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yao, Y. Huang, K. Shioi, K. Hattori, T. Murakami, N. Nakaigawa, T. Kishida, Y. Nagashima, and Y. Kubota Expression of Adipose Differentiation-Related Protein: A Predictor of Cancer-Specific Survival in Clear Cell Renal Carcinoma Clin. Cancer Res., January 1, 2007; 13(1): 152 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Shioi, A. Komiya, K. Hattori, Y. Huang, F. Sano, T. Murakami, N. Nakaigawa, T. Kishida, Y. Kubota, Y. Nagashima, et al. Vascular Cell Adhesion Molecule 1 Predicts Cancer-Free Survival in Clear Cell Renal Carcinoma Patients Clin. Cancer Res., December 15, 2006; 12(24): 7339 - 7346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Iliopoulos Molecular Biology of Renal Cell Cancer and the Identification of Therapeutic Targets J. Clin. Oncol., December 10, 2006; 24(35): 5593 - 5600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Banks, P. Tirukonda, C. Taylor, N. Hornigold, D. Astuti, D. Cohen, E. R. Maher, A. J. Stanley, P. Harnden, A. Joyce, et al. Genetic and Epigenetic Analysis of von Hippel-Lindau (VHL) Gene Alterations and Relationship with Clinical Variables in Sporadic Renal Cancer Cancer Res., February 15, 2006; 66(4): 2000 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. I. Rini VEGF-Targeted Therapy in Metastatic Renal Cell Carcinoma Oncologist, March 1, 2005; 10(3): 191 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Rini and E. J. Small Biology and Clinical Development of Vascular Endothelial Growth Factor-Targeted Therapy in Renal Cell Carcinoma J. Clin. Oncol., February 10, 2005; 23(5): 1028 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Y. Kim and W. G. Kaelin Role of VHL Gene Mutation in Human Cancer J. Clin. Oncol., December 15, 2004; 22(24): 4991 - 5004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. Rathmell, M. M. Hickey, N. A. Bezman, C. A. Chmielecki, N. C. Carraway, and M. C. Simon In vitro and In vivo Models Analyzing von Hippel-Lindau Disease-Specific Mutations Cancer Res., December 1, 2004; 64(23): 8595 - 8603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Curti Renal Cell Carcinoma JAMA, July 7, 2004; 292(1): 97 - 100. [Full Text] [PDF]
|
|
|
|
|
|
B. I. Rini, S. Halabi, J. Taylor, E. J. Small, and R. L. Schilsky Cancer and Leukemia Group B 90206: A Randomized Phase III Trial of Interferon-{alpha} or Interferon-{alpha} Plus Anti-Vascular Endothelial Growth Factor Antibody (Bevacizumab) in Metastatic Renal Cell Carcinoma Clin. Cancer Res., April 15, 2004; 10(8): 2584 - 2586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Zhou, H. Wang, R. L. Foy, J. J. Ross, and H. T. Cohen Tumor Suppressor von Hippel-Lindau (VHL) Stabilization of Jade-1 Protein Occurs through Plant Homeodomains and Is VHL Mutation Dependent Cancer Res., February 15, 2004; 64(4): 1278 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Abdel-Majid and J. S. Marshall Prostaglandin E2 Induces Degranulation-Independent Production of Vascular Endothelial Growth Factor by Human Mast Cells J. Immunol., January 15, 2004; 172(2): 1227 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hernberg, P. Virkkunen, P. Bono, H. Ahtinen, H. Maenpaa, and H. Joensuu Interferon Alfa-2b Three Times Daily and Thalidomide in the Treatment of Metastatic Renal Cell Carcinoma J. Clin. Oncol., October 15, 2003; 21(20): 3770 - 3776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Schraml, A. Hergovitz, F. Hatz, M. B. Amin, S. D. Lim, W. Krek, M. J. Mihatsch, and H. Moch Relevance of Nuclear and Cytoplasmic von Hippel Lindau Protein Expression for Renal Carcinoma Progression Am. J. Pathol., September 1, 2003; 163(3): 1013 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Khoo, K. Kahnoski, J. Sugimura, D. Petillo, J. Chen, K. Shockley, J. Ludlow, R. Knapp, S. Giraud, S. Richard, et al. Inactivation of BHD in Sporadic Renal Tumors Cancer Res., August 1, 2003; 63(15): 4583 - 4587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Redman, P. Esper, Q. Pan, R. L. Dunn, H. K. Hussain, T. Chenevert, G. J. Brewer, and S. D. Merajver Phase II Trial of Tetrathiomolybdate in Patients with Advanced Kidney Cancer Clin. Cancer Res., May 1, 2003; 9(5): 1666 - 1672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J C C Rocha, R L A Silva, B B Mendonca, S Marui, A J G Simpson, and A A Camargo High frequency of novel germline mutations in the VHL gene in the heterogeneous population of Brazil J. Med. Genet., March 1, 2003; 40(3): e31 - 31. [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Choyke, G. M. Glenn, M. M. Walther, B. Zbar, and W. M. Linehan Hereditary Renal Cancers Radiology, January 1, 2003; 226(1): 33 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Murata, N. Tajima, Y. Nagashima, M. Yao, M. Baba, M. Goto, S. Kawamoto, I. Yamamoto, K. Okuda, and H. Kanno Von Hippel-Lindau Tumor Suppressor Protein Transforms Human Neuroblastoma Cells into Functional Neuron-like Cells Cancer Res., December 1, 2002; 62(23): 7004 - 7011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yao, M. Yoshida, T. Kishida, N. Nakaigawa, M. Baba, K. Kobayashi, T. Miura, M. Moriyama, Y. Nagashima, Y. Nakatani, et al. VHL Tumor Suppressor Gene Alterations Associated With Good Prognosis in Sporadic Clear-Cell Renal Carcinoma J Natl Cancer Inst, October 16, 2002; 94(20): 1569 - 1575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. N. Otis, P. A. Krebs, A. Albuquerque, M. M. Quezado, X. S. Juan, M. E. Sobel, and M. J. Merino Loss of Heterozygosity of p53, BRCA1, VHL, and Estrogen Receptor Genes in Breast Carcinoma: Correlation with Related Protein Products and Morphologic Features International Journal of Surgical Pathology, October 1, 2002; 10(4): 237 - 245. [Abstract] [PDF]
|
|
|
|
 |
|
 Z. Li, X. Na, D. Wang, S. R. Schoen, E. M. Messing, and G. Wu Ubiquitination of a Novel Deubiquitinating Enzyme Requires Direct Binding to von Hippel-Lindau Tumor Suppressor Protein J. Biol. Chem., February 8, 2002; 277(7): 4656 - 4662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Pioli and W. F. C. Rigby The Von Hippel-Lindau Protein Interacts with Heteronuclear Ribonucleoprotein A2 and Regulates Its Expression J. Biol. Chem., October 19, 2001; 276(43): 40346 - 40352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Morrissey, A. Martinez, M. Zatyka, A. Agathanggelou, S. Honorio, D. Astuti, N. V. Morgan, H. Moch, F. M. Richards, T. Kishida, et al. Epigenetic Inactivation of the RASSF1A 3p21.3 Tumor Suppressor Gene in Both Clear Cell and Papillary Renal Cell Carcinoma Cancer Res., October 1, 2001; 61(19): 7277 - 7281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yang and W. G. Kaelin Jr. Molecular Pathogenesis of the Von Hippel-Lindau Hereditary Cancer Syndrome: Implications for Oxygen Sensing Cell Growth Differ., September 1, 2001; 12(9): 447 - 455. [Full Text] [PDF]
|
|
|
|
|
|
M. Velickovic, B. Delahunt, S. Storkel, and S. K. G. Grebem VHL and FHIT Locus Loss of Heterozygosity Is Common in All Renal Cancer Morphotypes But Differs in Pattern and Prognostic Significance Cancer Res., June 1, 2001; 61(12): 4815 - 4819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kamada, K. Suzuki, Y. Kato, H. Okuda, and T. Shuin von Hippel-Lindau Protein Promotes the Assembly of Actin and Vinculin and Inhibits Cell Motility Cancer Res., May 1, 2001; 61(10): 4184 - 4189. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. Konishi, M. Nakamura, E. Ishida, Y. Kawada, M. Nishimine, H. Nagai, and M. Emi Specific Genomic Alterations in Rat Renal Cell Carcinomas Induced by N-Ethyl-N-hydroxyethylnitrosamine Toxicol Pathol, February 1, 2001; 29(2): 232 - 236. [Abstract] [PDF]
|
|
|
|
 |
|
 B. U. Bender, M. Gutsche, S. Gläsker, B. Müller, G. Kirste, C. Eng, and H. P. H. Neumann Differential Genetic Alterations in von Hippel-Lindau Syndrome-Associated and Sporadic Pheochromocytomas J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4568 - 4574. [Abstract] [Full Text]
|
|
|
|
|
|
S. Ashida, H. Okuda, M. Chikazawa, M. Tanimura, O. Sugita, Y. Yamamoto, S. Nakamura, M. Moriyama, and T. Shuin Detection of Circulating Cancer Cells with von Hippel-Lindau Gene Mutation in Peripheral Blood of Patients with Renal Cell Carcinoma Clin. Cancer Res., October 1, 2000; 6(10): 3817 - 3822. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. L. Semenza HIF-1 and human disease: one highly involved factor Genes & Dev., August 15, 2000; 14(16): 1983 - 1991. [Full Text]
|
|
|
|
 |
|
 A Martinez, P Fullwood, K Kondo, T Kishida, M Yao, E R Maher, and F Latif Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell carcinoma: analysis of VHL dependent and VHL independent pathways of tumorigenesis Mol. Pathol., June 1, 2000; 53(3): 137 - 144. [Abstract] [Full Text]
|
|
|
|
|
|
H. Kanno, F. Saljooque, I. Yamamoto, S. Hattori, M. Yao, T. Shuin, and H.-S. U Role of the von Hippel-Lindau Tumor Suppressor Protein during Neuronal Differentiation Cancer Res., June 1, 2000; 60(11): 2820 - 2824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R Woodward, S. C Clifford, D. Astuti, N. A Affara, and E. R Maher Familial clear cell renal cell carcinoma (FCRC): clinical features and mutation analysis of the VHL, MET, and CUL2 candidate genes J. Med. Genet., May 1, 2000; 37(5): 348 - 353. [Abstract] [Full Text]
|
|
|
|
|
|
H. Brauch, G. Weirich, J. Brieger, D. Glavac, H. Rödl, M. Eichinger, M. Feurer, E. Weidt, C. Puranakanitstha, C. Neuhaus, et al. VHL Alterations in Human Clear Cell Renal Cell Carcinoma: Association with Advanced Tumor Stage and a Novel Hot Spot Mutation Cancer Res., April 1, 2000; 60(7): 1942 - 1948. [Abstract] [Full Text]
|
|
|
|
|
|
H. Brauch, G. Weirich, M. A. Hornauer, S. Storkel, T. Wohl, and T. Bruning Trichloroethylene Exposure and Specific Somatic Mutations in Patients With Renal Cell Carcinoma J Natl Cancer Inst, May 19, 1999; 91(10): 854 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Stebbins, W. G. Kaelin Jr., and N. P. Pavletich Structure of the VHL-ElonginC-ElonginB Complex: Implications for VHL Tumor Suppressor Function Science, April 16, 1999; 284(5413): 455 - 461. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Lee, M. Neumann, R. Stearman, R. Stauber, A. Pause, G. N. Pavlakis, and R. D. Klausner Transcription-Dependent Nuclear-Cytoplasmic Trafficking Is Required for the Function of the von Hippel-Lindau Tumor Suppressor Protein Mol. Cell. Biol., February 1, 1999; 19(2): 1486 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Iliopoulos, M. Ohh, and W. G. Kaelin Jr. pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation PNAS, September 29, 1998; 95(20): 11661 - 11666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Lonergan, O. Iliopoulos, M. Ohh, T. Kamura, R. C. Conaway, J. W. Conaway, and W. G. Kaelin Jr. Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2 Mol. Cell. Biol., February 1, 1998; 18(2): 732 - 741. [Abstract] [Full Text]
|
|
|
|
|
|
C. Walker Molecular Genetics of Renal Carcinogenesis Toxicol Pathol, January 1, 1998; 26(1): 113 - 120. [Abstract] [PDF]
|
|
|
|
|
|
A. Pause, S. Lee, R. A. Worrell, D. Y. T. Chen, W. H. Burgess, W. M. Linehan, and R. D. Klausner The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins PNAS, March 18, 1997; 94(6): 2156 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. J. Weterman, M. Wilbrink, and A. G. van Kessel Fusion of the transcription factor TFE3 gene to a novel gene, PRCC, in t(X;1)(p11;q21)-positive papillary renal cell carcinomas PNAS, December 24, 1996; 93(26): 15294 - 15298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Duan, A Pause, W. Burgess, T Aso, D. Chen, K. Garrett, R. Conaway, J. Conaway, W. Linehan, and R. Klausner Inhibition of transcription elongation by the VHL tumor suppressor protein Science, September 8, 1995; 269(5229): 1402 - 1406. [Abstract] [PDF]
|
|
|
|
|
|
A Kibel, O Iliopoulos, J. DeCaprio, and W. Kaelin Jr Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C Science, September 8, 1995; 269(5229): 1444 - 1446. [Abstract] [PDF]
|
|
|
|
|
|
W. M. Linehan, M. I. Lerman, and B. Zbar Identification of the von Hippel-Lindau (VHL) Gene: Its Role in Renal Cancer JAMA, February 15, 1995; 273(7): 564 - 570. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
