Aberrant DNA Methylation and Histone Modifications in Cancer

Abstract

DNA (deoxyribonucleic acid) methylation of cytosines in CpG dinucleotides and post‐translational modifications of histone amino acids are epigenetic mechanisms that are in normal cells involved in specific cell functions, particularly in regulation of transcription and maintenance of stable chromatin. The epigenetic code is highly dynamic and enables the cells to regulate their responses to the intrinsic or environmental signals. Aberrations of DNA methylation patterns and histone modifications are major features observed in all types of cancer. Integrated research of genomic alterations, erroneous gene expression and modifications of epigenomes in cancer cells has revealed the complexity and heterogeneity of this disease. Some of the novel therapeutic and diagnostic approaches based on aberrant promoter hypermethylation and histone modifications, particularly acetylation, have already been translated into a clinical setting, whereas a number of others are being examined in clinical trials. Key Concepts DNA methylation and histone modifications cooperate in regulation of certain cell functions and responses. Cancer development and progression are characterised by diverse aberrations in epigenetic profiles. Changes in DNA methylation profiles could be used to define specific subsets of cancers, which harbour characteristic genetic alterations. Hypermethylation or hypomethylation of gene promoters, resulting in silencing or activating the gene transcription, respectively, are fundamental in the identification of novel tumour suppressors and oncogenes. Unravelling the functional consequences of methylation signature in nonpromoter regions is complex and will require further research efforts to discern their role in healthy and diseased cells. Epigenetic profiling of cancers has already identified and is still identifying novel targets for the development of therapeutic and diagnostic approaches.