Epigenetics and Cancer
Epigenetic characteristics are heritable features, propagated through cell division, that contribute to cellular identity independent of DNA sequence. Such characteristics include DNA methylation, covalent histone modifications, and non-coding RNA-depende
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Epigenetics and Cancer Andrew D. Kelly and Jean-Pierre J. Issa
Abstract Epigenetic characteristics are heritable features, propagated through cell division, that contribute to cellular identity independent of DNA sequence. Such characteristics include DNA methylation, covalent histone modifications, and noncoding RNA-dependent gene regulation. Over the past few decades, epigenetic changes in cancer have become recognized and widely accepted as important contributors to malignant transformation. Such alterations result in a transcriptional program that promotes molecular diversity and provides a selective advantage to cancer cells through tumor suppressor gene silencing and aberrant oncogene activation. Causes of epigenetic aberrations remain under active investigation and include at least stochastic changes associated with aging, mutations in epigenetic modifying enzymes, and altered cellular metabolism through changing the metabolite repertoire. A number of therapies targeting epigenetic modifiers have been approved by the FDA for cancer treatment, and many others are in clinical trials. Ongoing research is focused on better understanding mechanisms contributing to the altered epigenome, how the altered epigenome contributes to malignant transformation, and how epigenetic therapies can be best applied clinically to patients most likely to benefit from them. Keywords Epigenetics • DNA methylation • Histone modification • Non-coding RNA • Epigenetic therapy • Precision medicine
A.D. Kelly Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, PAHB 339, 3307 N. Broad St., Philadelphia, PA 19140, USA e-mail: [email protected] J.-P. J. Issa (*) Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, PAHB 154 3307 N. Broad St., Philadelphia, PA 19140, USA e-mail: [email protected] © Springer International Publishing Switzerland 2016 N.A. Berger (ed.), Epigenetics, Energy Balance, and Cancer, Energy Balance and Cancer 11, DOI 10.1007/978-3-319-41610-6_1
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A.D. Kelly and J.-P. J. Issa
Background Epigenetics can be broadly defined as the biological mechanisms governing cellular identity and heritable phenotypes arising from characteristics other than DNA sequence [1, 2]. These distinct phenotypes arise as a result of epigenetic regulation of gene expression, which falls into several major categories: DNA methylation, histone modification, and non-coding RNA-dependent regulation (Table 1.1).
DNA Methylation Characteristics of DNA Methylation Methylation refers to the biochemical process of adding a methyl group to a molecule. In mammals, DNA methylation occurs predominantly at the five position of cytosine residues within CG dinucleotides and is distributed in specific genomic compartments [3]: CpG islands are regions of high CG dinucleotide density that lie near the promoters of up to 70 % of genes and are unmethylated under normal conditions [3–5]. CpG island methylation status has been causally link
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