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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transl Med. Apr 12, 2015; 4(1): 11-24
Published online Apr 12, 2015. doi: 10.5528/wjtm.v4.i1.11
Epigenetics and DNA methylation in cancer
Laura Lattanzio, Cristiana Lo Nigro
Laura Lattanzio, Cristiana Lo Nigro, Laboratory Cancer Genetics and Translational Oncology, Medical Oncology, S. Croce University Hospital, 12100 Cuneo, Italy
Author contributions: Lattanzio L and Lo Nigro C contributed to this paper.
Conflict-of-interest: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Cristiana Lo Nigro, PhD, Laboratory Cancer Genetics and Translational Oncology, Medical Oncology, S. Croce University Hospital, Via Carle 25, 12100 Cuneo, Italy. lonigro.c@ospedale.cuneo.it
Telephone: +39-0171-616338 Fax: +39-0171-616331
Received: August 8, 2014
Peer-review started: August 9, 2014
First decision: October 14, 2014
Revised: February 19, 2015
Accepted: March 18, 2015
Article in press: March 20, 2015
Published online: April 12, 2015
Processing time: 249 Days and 1.5 Hours
Abstract

Epigenetic is the study of those alterations regulating gene expression without altering DNA sequence and inherited by transmission through cell division. Mutational and epimutational events that alterate cellular growth and division are combined in carcinogenesis. Advances in genome and epigenome-wide analysis identify DNA hypomethylation, hypermethylation of tumor suppressor genes, aberrant histone modifications and/or specific miRNA expression profiles to contribute to tumor initiation and progression. The major challenge for cancer researchers is to enlighten the complex relationship between the epigenetic and genetic machinery in order to optimize combined therapies, reducing chemoresistance and minimizing adverse effects in cancer patients. In this review we will cover many distinct aspects of epigenetic phenomenon. Firstly, we will globally explain the most common epigenetic events and their effects on gene expression regulation. Secondly, we will review the evidence of the correlation between epigenetics and cancer progression, focusing in particular on the effect of aberrant hypo- and hyper-methylation. We will also consider the main methods currently used for methylation analysis, covering both locus-specific technologies and genome-wide analysis. Finally, we will discuss the introduction of novel epigenetic drugs in combination with conventional treatments in order to develop more effective cancer therapies. Such information could help in understanding the important role of epigenetics in cancer.

Keywords: Epigenetics; DNA methylation; Cancer; Regulation of transcription; Prognostic markers

Core tip: Carcinogenesis occurs through a combination of mutational and epimutational alterations involving key pathways in cellular growth and division. Tumour cells exhibit two main differences from normal cells in DNA methylation: a global reduction in DNA methylation and the hypermethylation of specific sequences, mainly CpG islands, that cause the transcriptional silencing of tumour suppressor genes, thus directly driving the carcinogenic. In this review, we’ll focus on our current understanding of this process, aiming to discuss how the analysis of cancer methylomes and the re-expression of epigenetically silenced genes have potential uses in developing more effective cancer therapies.