Alterations in VHL as potential biomarkers in renal-cell carcinoma

Nature Reviews Clinical Oncology

Volumn 7, Issue 5, 2010, Pages 277-288

  Gossage, Lucy ^a   Eisen, Tim ^b  

^a CANCER RESEARCH UK CAMBRIDGE RESEARCH INSTITUTE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; AXITINIB; BEVACIZUMAB; BIOLOGICAL MARKER; CARBONATE DEHYDRATASE IX; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; MESSENGER RNA; PAZOPANIB; POLYUBIQUITIN; PROTEOME; SORAFENIB; SUNITINIB; TEMSIROLIMUS; UBIQUITIN PROTEIN LIGASE; VON HIPPEL LINDAU PROTEIN;

CANCER RISK; CLINICAL TRIAL; COMPLEX FORMATION; DISEASE ASSOCIATION; DISEASE MARKER; GENE OVEREXPRESSION; GENETIC ASSOCIATION; GENOTYPE PHENOTYPE CORRELATION; HUMAN; KIDNEY CARCINOMA; MUTATIONAL ANALYSIS; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; RNA TRANSCRIPTION; TUMOR SUPPRESSOR GENE; VON HIPPEL LINDAU DISEASE;

BIOLOGICAL MARKERS; CARCINOMA, RENAL CELL; DNA METHYLATION; GENETIC ASSOCIATION STUDIES; GERM-LINE MUTATION; HUMANS; PHEOCHROMOCYTOMA; PROTEINS; RISK FACTORS; VON HIPPEL-LINDAU DISEASE;

EID: 77951877765     PISSN: 17594774     EISSN: 17594782     Source Type: Journal    
DOI: 10.1038/nrclinonc.2010.42     Document Type: Review

References (81)

1. Kaelin, W. G. Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat. Rev. Cancer 2, 673-682 (2002). (Pubitemid 37328918)
2. Maher, E. R. et al. Clinical features and natural history of von Hippel-Lindau disease. Q. J. Med. 77, 1151-1163 (1990). (Pubitemid 20379533)
3. Gnarra, J. R. et al. Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. Proc. Natl Acad. Sci. USA 93, 10589-10594 (1996).
4. Iliopoulos, O., Kibel, A., Gray, S. & Kaelin, W. G. Jr. Tumor suppression by the human von Hippel-Lindau gene product. Nat. Med. 1, 822-826 (1995).
5. Schoenfeld, A., Davidowitz, E. J. & Burk, R. D. A second major native von Hippel-Lindau gene product, initiated from an internal translation start site, functions as a tumor suppressor. Proc. Natl Acad. Sci. USA 95, 8817-8822 (1998). (Pubitemid 28350572)
6. Davidowitz, E. J., Schoenfeld, A. R. & Burk, R. D. VHL induces renal cell differentiation and growth arrest through integration of cell-cell and cell-extracellular matrix signaling. Mol. Cell. Biol. 21, 865-874 (2001).
7. Lieubeau-Teillet, B. et al. von Hippel-Lindau gene-mediated growth suppression and induction of differentiation in renal cell carcinoma cells grown as multicellular tumor spheroids. Cancer Res. 58, 4957-4962 (1998). (Pubitemid 28503696)
8. Pause, A., Lee, S., Lonergan, K. M. & Klausner, R. D. The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal. Proc. Natl Acad. Sci. USA 95, 993-998 (1998). (Pubitemid 28124900)
9. Knudson, A. G. Jr. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl Acad. Sci. USA 68, 820-823 (1971).
10. Foster, K. et al. Somatic mutations of the von Hippel-Lindau disease tumor suppressor gene in non-familial clear cell renal carcinoma. Hum. Mol. Genet. 3, 2169-2173 (1994).
11. Gnarra, J. R. et al. Mutations of the VHL tumor suppressor gene in renal carcinoma. Nat. Genet. 7, 85-90 (1994).
12. Shuin, T. et al. Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. Cancer Res. 54, 2852-2855 (1994). (Pubitemid 24187761)
13. Whaley, J. M. et al. Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma. Am. J. Hum. Genet. 55, 1092-1102 (1994).
14. Cockman, M. E. et al. Hypoxia inducible factoralpha binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 275, 25733-25741 (2000).
15. Kamura, T. et al. Activation of HIF-1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc. Natl Acad. Sci. USA 97, 10430-10435 (2000).
16. Maxwell, P. H. et al. The tumor suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271-275 (1999).
17. Ohh, M. et al. Ubiquitination of hypoxiainducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat. Cell Biol. 2, 423-427 (2000).
18. Tanimoto, K., Makino, Y., Pereira, T. & Poellinger, L. Mechanism of regulation of the hypoxia-inducible factor-1α by the von Hippel-Lindau tumor suppressor protein. EMBO J. 19, 4298-4309 (2000). (Pubitemid 30623741)
19. Kaelin, W. G. The von Hippel-Lindau tumor suppressor protein: roles in cancer and oxygen sensing. Cold Spring Harbor Symp. Quant. Biol. 70, 159-166 (2005).
20. Kaelin, W. G. Jr. The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing. Biochem. Biophys. Res. Commun. 338, 627-638 (2005).
21. Kaelin, W. G. Jr. The von Hippel-Lindau tumor suppressor protein: an update. Methods Enzymol. 435, 371-383 (2007).
22. Kaelin, W. G. Jr. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin. Cancer Res. 13 (Pt 2), 680s-684s (2007).
23. 2 sensing and cancer. Nat. Rev. Cancer 8, 865-873 (2008).
24. Kaelin, W. G. Von Hippel-Lindau disease. Annu. Rev. Pathol. 2, 145-173 (2007). (Pubitemid 46463864)
25. Nyhan, M. J., O'Sullivan, G. C. & McKenna, S. L. Role of the VHL (von Hippel-Lindau) gene in renal cancer: a multifunctional tumor suppressor. Biochem. Soc. Trans. 36 (Pt 3), 472-478 (2008).
26. Frew, I. J. & Krek, W. Multitasking by pVHL in tumor suppression. Curr. Opin. Cell Biol. 19, 685-690 (2007).
27. Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182-1186 (1971).
28. Cébe-Suarez, S., Zehnder-Fjällman, A. & Ballmer-Hofer, K. The role of VEGF receptors in angiogenesis; complex partnerships. Cell. Mol. Life Sci. 63, 601-615 (2006).
29. Bastien, L. et al. Targeted therapies in metastatic renal cancer in 2009. BJU Int. 103, 1334-1342 (2009).
30. Atkins, M. B. et al. Innovations and challenges in renal cancer: summary statement from the Third Cambridge Conference. Cancer 115 (Suppl.), 2247-2251 (2009).
31. Kaelin, W. G. Jr. Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein. Cancer 115 (Suppl.), 2262-2272 (2009).
32. Motzer, R. J., Bacik, J., Murphy, B. A., Russo, P. & Mazumdar, M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J. Clin. Oncol. 20, 289-296 (2002). (Pubitemid 34032623)
33. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783-792 (2001).
34. Lievre, A. et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 66, 3992-3995 (2006).
35. Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129-2139 (2004). (Pubitemid 38637993)
36. Ong, K. R. et al. Genotype-phenotype correlations in von Hippel-Lindau disease. Hum. Mutat. 28, 143-149 (2007). (Pubitemid 46233311)
37. Forman, J. R., Worth, C. L., Bickerton, G. R., Eisen, T. G. & Blundell, T. L. Structural bioinformatics mutation analysis reveals genotype-phenotype correlations in von Hippel-Lindau disease and suggests molecular mechanisms of tumorigenesis. Proteins 77, 84-96 (2009).
38. Clifford, S. C. et al. Contrasting effects on HIF-1α regulation by disease-causing pVHL mutations correlate with patterns of tumorigenesis in von Hippel-Lindau disease. Hum. Mol. Genet. 10, 1029-1038 (2001).
39. Molina, A. M. & Motzer, R. J. Current algorithms and prognostic factors in the treatment of metastatic renal cell carcinoma. Clin. Genitourin. Cancer 6 (Suppl. 1), S7-S13 (2008).
40. Knauth, K., Bex, C., Jemth, P. & Buchberger, A. Renal cell carcinoma risk in type 2 von Hippel-Lindau disease correlates with defects in pVHL stability and HIF-1α interactions. Oncogene 25, 370-377 (2006). (Pubitemid 43117622)
41. Li, L. et al. Hypoxia-inducible factor linked to differential kidney cancer risk seen with type 2A and type 2B VHL mutations. Mol. Cell Biol. 27, 5381-5392 (2007). (Pubitemid 47124392)
42. Pastore, Y. D. et al. Mutations in the VHL gene in sporadic apparently congenital polycythemia. Blood 101, 1591-1595 (2003). (Pubitemid 36182539)
43. Ang, S. O. et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat. Genet. 32, 614-621 (2002).
44. Banks, R. E. et al. Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer. Cancer Res. 66, 2000-2011 (2006). (Pubitemid 43294908)
45. Brauch, H. et al. VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation. Cancer Res. 60, 1942-1948 (2000). (Pubitemid 30207656)
46. Giménez-Bachs, J. M. et al. VHL protein alterations in sporadic renal cell carcinoma. Clin. Oncol. (R. Coll. Radiol.) 19, 784-789 (2007).
47. Kim, J. H. et al. Somatic VHL alteration and its impact on prognosis in patients with clear cell renal cell carcinoma. Oncol. Rep. 13, 859-864 (2005).
48. Kondo, K. et al. Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters. Genes Chromosomes Cancer 34, 58-68 (2002). (Pubitemid 34260597)
49. Ma, X., Yang, K., Lindblad, P., Egevad, L. & Hemminki, K. VHL gene alterations in renal cell carcinoma patients: novel hotspot or founder mutations and linkage disequilibrium. Oncogene 20, 5393-5400 (2001). (Pubitemid 32844071)
50. Nickerson, M. L. et al. Improved identification of von Hippel-Lindau gene alterations in clear cell renal tumors. Clin. Cancer Res. 14, 4726-4734 (2008).
51. Patard, J. J. et al. Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. Int. J. Cancer 123, 395-400 (2008).
52. Schraml, P. et al. VHL mutations and their correlation with tumor cell proliferation, microvessel density, and patient prognosis in clear cell renal cell carcinoma. J. Pathol. 196, 186-193 (2002). (Pubitemid 34110900)
53. Smits, K. M. et al. Genetic and epigenetic alterations in the von Hippel-Lindau gene: the influence on renal cancer prognosis. Clin. Cancer Res. 14, 782-787 (2008).
54. Suzuki, H. et al. Mutational state of von Hippel-Lindau and adenomatous polyposis coli genes in renal tumors. Oncology 54, 252-257 (1997). (Pubitemid 27160594)
55. van Houwelingen, K. P. et al. Prevalence of von Hippel-Lindau gene mutations in sporadic renal cell carcinoma: results from The Netherlands cohort study. BMC Cancer 5, 57 (2005).
56. Yao, M. et al. VHL tumor suppressor gene alterations associated with good prognosis in sporadic clear-cell renal carcinoma. J. Natl Cancer Inst. 94, 1569-1575 (2002). (Pubitemid 35277281)
57. Choyke, P. L. et al. The natural history of renal lesions in von Hippel-Lindau disease: a serial CT study in 28 patients. AJR Am. J. Roentgenol. 159, 1229-1234 (1992).
58. Neumann, H. P. et al. Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma. J. Urol. 160, 1248-1254 (1998). (Pubitemid 29480491)
59. Gallou, C. et al. Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions. Hum. Mutat. 24, 215-224 (2004). (Pubitemid 39095598)
60. Yang, K., Lindblad, P., Egevad, L. & Hemminki, K. Novel somatic mutations in the VHL gene in Swedish archived sporadic renal cell carcinomas. Cancer Lett. 141, 1-8 (1999). (Pubitemid 29261715)
61. Gordan, J. D. et al. HIF-α effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell 14, 435-446 (2008).
62. Smaldone, M. C. & Maranchie, J. K. Clinical implications of hypoxia inducible factor in renal cell carcinoma. Urol. Oncol. 27, 238-245 (2009).
63. Kondo, K., Kim, W. Y., Lechpammer, M. & Kaelin, W. G. Jr. Inhibition of HIF2α is sufficient to suppress pVHL-defective tumor growth. PLoS Biol. 1, E83 (2003). (Pubitemid 39112142)
64. -/- tumors. Mol. Cancer Res. 2, 89-95 (2004). (Pubitemid 38250425)
65. Kondo, K., Klco, J., Nakamura, E., Lechpammer, M. & Kaelin, W. G. Jr. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 1, 237-246 (2002). (Pubitemid 41039148)
66. Maranchie, J. K. et al. The contribution of VHL substrate binding and HIF-1α to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 1, 247-255 (2002).
67. Hoffman, M. A. et al. von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF. Hum. Mol. Genet. 10, 1019-1027 (2001).
68. Hu, C. J., Wang, L. Y., Chodosh, L. A., Keith, B. & Simon, M. C. Differential roles of hypoxiainducible factor 1α (HIF-1α) and HIF-2α in hypoxic gene regulation. Mol. Cell Biol. 23, 9361-9374 (2003). (Pubitemid 37499822)
69. Raval, R. R. et al. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol. Cell Biol. 25, 5675-5686 (2005). (Pubitemid 40853601)
70. Zimmer, M. et al. Small-molecule inhibitors of HIF-2α translation link its 5'UTR iron-responsive element to oxygen sensing. Mol. Cell. 32, 838-848 (2008).
71. Bui, M. H. et al. Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. Clin. Cancer Res. 9, 802-811 (2003).
72. Choueiri, T. K. et al. von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. J. Urol. 180, 860-866 (2008).
73. Rini, B. I. et al. Clinical response to therapy targeted at vascular endothelial growth factor in metastatic renal cell carcinoma: impact of patient characteristics and von Hippel-Lindau gene status. BJU Int. 98, 756-762 (2006).
74. Gad, S. et al. Somatic von Hippel-Lindau (VHL) gene analysis and clinical outcome under antiangiogenic treatment in metastatic renal cell carcinoma: preliminary results. Targeted Oncology 2, 3-6 (2007).
75. Hutson, T. E. et al. Biomarker analysis and final efficacy and safety results of a phase II renal cell carcinoma trial with pazopanib (GW786034), a multi-kinase angiogenesis inhibitor. J. Clin. Oncol. 26 (Suppl.), 5046 (2008).
76. Cho, D. et al. Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Clin. Genitourin. Cancer 5, 379-385 (2007). (Pubitemid 47584475)
77. Atkins, M. et al. Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin. Cancer Res. 11, 3714-3721 (2005). (Pubitemid 40685588)
78. Beroukhim, R. et al. Patterns of gene expression and copy-number alterations in von Hippel-Lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res. 69, 4674-4681 (2009).
79. Carmeliet, P. VEGF as a key mediator of angiogenesis in cancer. Oncology 69 (Suppl. 3), 4-10 (2005). (Pubitemid 41680947)
80. Poon, E., Harris, A. L. & Ashcroft, M. Targeting the hypoxia-inducible factor (HIF) pathway in cancer. Expert Rev. Mol. Med. 11, e26 (2009).
81. Koh, M. Y. & Powis, G. HAF: the new player in oxygen-independent HIF-1α degradation. Cell Cycle 8, 1359-1366 (2009).