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Int. J. Mol. Sci. 2017, 18(8), 1774;

Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma

Department of Human Genetics, McGill University, 1205 Dr Penfield Avenue, Montreal, QC H3A 1B1, Canada
McGill University and Genome Quebec Innovation Centre, 740 Dr Penfield Avenue, Montreal, QC H3A 0G1, Canada
Author to whom correspondence should be addressed.
Received: 6 July 2017 / Revised: 29 July 2017 / Accepted: 12 August 2017 / Published: 16 August 2017
(This article belongs to the Special Issue Cancer Epigenetics)
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Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC. Although VHL mutations are considered as drivers of ccRCC, they are not sufficient to cause the disease. Recent genome-wide sequencing studies of ccRCC have revealed that mutations of genes coding for epigenome modifiers and chromatin remodelers, including PBRM1, SETD2 and BAP1, are the most common somatic genetic abnormalities after VHL mutations in these tumors. Moreover, recent research has shed light on the extent of abnormal epigenome alterations in ccRCC tumors, including aberrant DNA methylation patterns, abnormal histone modifications and deregulated expression of non-coding RNAs. In this review, we discuss the epigenetic modifiers that are commonly mutated in ccRCC, and our growing knowledge of the cellular processes that are impacted by them. Furthermore, we explore new avenues for developing therapeutic approaches based on our knowledge of epigenome aberrations of ccRCC. View Full-Text
Keywords: renal cell carcinoma; DNA methylation; histone modifications; lncRNA; HIF; VHL; ccRCC; epigenetic therapy renal cell carcinoma; DNA methylation; histone modifications; lncRNA; HIF; VHL; ccRCC; epigenetic therapy

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Mehdi, A.; Riazalhosseini, Y. Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma. Int. J. Mol. Sci. 2017, 18, 1774.

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