Role of DNA methylation in renal cell carcinoma. - Beyond the Abstract

Over the last decade, the role of epigenetics in cancer progression has been studied extensively. Epigenetics is the study of heritable changes in gene expression without alteration of the DNA sequence. Epigenetic changes could involve chemical modification of DNA bases via methylation of cytosines, or histone protein modification, or regulation by non-coding RNAs. DNA methylation involves the addition of a methyl group at the 5-carbon position of the cytosine ring at CpG dinucleotides within a gene promoter and/or enhancer and is a common reversible epigenetic alteration that has been reported in many cancers.

Hypermethylation of promoter or enhancer CpG regions can result in inactivation of important tumor suppressor genes whereas hypomethylation of genomic DNA has been associated with chromosomal instability and tumorigenesis.

DNA methylation influences oncogenic driver pathways, cell cycle regulators, apoptosis, immune evasion, metabolism, DNA mismatch repair system, etc. thus playing an integral role in many aspects of kidney cancer progression. This article is a comprehensive review of the role of aberrant DNA methylation in kidney cancer. The degree of aberrant methylation in kidney cancer has also been shown to be prognostic for overall survival.[1] Hypomethylating agents have been shown to inhibit the proliferation of renal cell carcinoma both in vitro and in xenograft studies by the re-expression of numerous tumor suppressor genes silenced by enhancer/promoter hypermethylation.[2,3] Reversing the effects of widespread aberrant DNA hypermethylation with hypomethylating agents therefore is an exciting therapeutic strategy and is being explored in clinical trials in combination with other anticancer agents in renal cell cancer.(clinicaltrials.gov)

Written By: 

Niraj Shenoy, Nishanth Vallumsetla, Yiyu Zou, Jose Nahun Galeas, Makardhwaj Shrivastava, Caroline Hu, Katalin Susztak, Amit Verma

References:

Hu CY, et al. Kidney cancer is characterized by aberrant methylation of tissue-specific enhancers that are prognostic for overall survival. Clin Cancer Res. 2014;20(16):4349–4360. doi: 10.1158/1078-0432.CCR-14-0494
Hagiwara H, et al. 5-Aza-2′-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. Br J Pharmacol. 2008;153(7):1373–1381. doi: 10.1038/bjp.2008.17
Ricketts CJ, et al. Methylation profiling and evaluation of demethylating therapy in renal cell carcinoma. Clin Epigenetics

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