Larkin, J., Goh, X. Y., Vetter, M., Pickering, L., Swanton, C. (2012) Epigenetic regulation in RCC: opportunities for therapeutic intervention? NATURE REVIEWS UROLOGY, 9 (3). pp. 147-155. ISSN 1759-4812

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Abstract

Renal cell carcinoma (RCC) is a constellation of malignancies of different histological subtypes arising from the renal parenchyma. The clear cell histological subtype (ccRCC) accounts for around 75% of RCCs and is characterized by distinct genetic abnormalities, of which the loss of function of the von Hippel-Lindau (VHL) tumor suppressor gene is the most common. Inactivation of other tumor suppressor genes such as SETD2, KDM6A, KDM5C and PBRM1 has been reported in ccRCC-notably, the proteins encoded by these genes are involved in histone and chromatin regulation. Furthermore, the PBRM1 and SETD2 genes are located on the short arm of chromosome 3 near the VHL locus. Chromatin and histones modify gene expression and, as a consequence, their function is tightly regulated. Data from RNA interference (RNAi) assays suggest that loss of function of PBRM1 drives proliferation and growth of ccRCC, but the clinical relevance of this is unclear and restoring the function of these genes for therapeutic purposes is likely to be challenging. An improved understanding of histone and chromatin regulation in RCC biology and the consequences of intratumor heterogeneity might identify novel targets in RCC and present alternative therapeutic opportunities.

Item Type:	Review Article
All Authors:	Larkin, J., Goh, X. Y., Vetter, M., Pickering, L., Swanton, C.
Additional Information:	ISI Document Delivery No.: 906ZP Times Cited: 0 Cited Reference Count: 113 Larkin, James Goh, Xin Yi Vetter, Marcus Pickering, Lisa Swanton, Charles Nature publishing group New york
Uncontrolled Keywords:	renal-cell carcinoma histone deacetylase inhibitors phase-ii breast-cancer lung-cancer dna methylation chromatin modifications uterine leiomyomatosis fumarate hydratase lysine methylation
Research teams:	Clinical Units > Skin Unit
Depositing User:	Barry Jenkins
Date Deposited:	23 Apr 2012 12:31
Last Modified:	23 Apr 2012 12:31
URI:	http://publications.icr.ac.uk/id/eprint/11539

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