Tumor Biology

, Volume 33, Issue 1, pp 9–16

Role of VHL gene mutation in human renal cell carcinoma


DOI: 10.1007/s13277-011-0257-3

Cite this article as:
Arjumand, W. & Sultana, S. Tumor Biol. (2012) 33: 9. doi:10.1007/s13277-011-0257-3


The Von Hippel–Lindau (VHL) is an inherited neoplasia syndrome caused by the inactivation of VHL tumor suppressor gene, and somatic mutation of this gene has been related to the development of sporadic clear cell renal carcinoma. The affected individuals are at higher risk for the development of tumor in other organs, which include pheochromocytomas, retinal angioma, pancreatic cysts, and CNS hemangioblastomas. The VHL mRNA encodes a protein (pVHL) that contains 213 amino acid residues which migrate with an apparent molecular weight of 24 to 30 kDa. The VHL gene protein has multiple functions that are linked to tumor suppression, but the best recognized and evidently linked to the development of renal cell carcinoma (RCC) is inhibition of hypoxia-inducible factor (HIF), as well as plays a role in targeting HIF for ubiquitin-mediated degradation. Aberrations in VHL's function, either through mutation or promoter hypermethylation, lead to the accumulation of HIF, which will transcriptionally upregulate a sequence of hypoxia responsive genes, including epidermal growth factor, vascular endothelial growth factor, platelet-derived growth factor, and other proangiogenic factors, resulting in upregulated blood vessel growth, one of the prerequisites of a tumor. HIF plays a critical role in pVHL-defective tumor formation, raising the possibility that drugs directed against HIF or its downstream targets (such as vascular endothelial growth factor) may one day play a role in the treatment of RCC. Moreover, a number of drugs have been developed that target HIF-responsive gene products, many of these targeted therapies have demonstrated significant activity in kidney cancer clinical trials and signify substantive advances in the treatment of this disease.


Von Hippel–LindauHypoxia-inducible factorRenal cell carcinomaHypoxia response elementsVascular endothelial growth factor

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  1. 1.Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of ScienceJamia Hamdard (Hamdard University)New DelhiIndia