Aberrant Patterns of DNA Methylation in Cancer

Abstract

Abstract Deoxyribonucleic acid (DNA) methylation is an epigenetic mechanism involved in the regulation of gene expression and preservation of genome stability in normal cells. Alterations of DNA methylation code have been associated with the development and progression of many diseases, including cancer. Novel technologies allow genome‐wide interrogation of methylation patterns. Data on different types of cancer are accumulating; however, elucidation of the consequences of all observed demethylation or methylation events and understanding their associations with other genomic aberrations present great challenges for the future research. Nevertheless, several findings regarding gene silencing by hypermethylation of CpG islands in promoters of genes have been successfully transferred in clinical setting aiding in diagnosis or prognosis of different types of cancer. In addition, therapeutic application of small molecule inhibitors of DNA methyltransferases (DNMTs) to reverse epigenetic silencing has been proven to be beneficial for treatment of various cancers. Key Concepts Alterations of epigenetic mechanisms, including DNA methylation, are implicated in the pathogenesis of many diseases, including cancer. DNA methylation of CpG dinucleotides distributed in the genome can either repress or enable transcription of genes, depending on the location of CpGs and the level of methylation. DNA methylation can be influenced by different internal and external factors, which contribute to the establishment of heterogeneous DNA methylation patterns in cancers. Observed heterogeneity of methylation profiles between tumours and within tumours represents an obstacle in obtaining relevant biological information that could be translated into the knowledge of molecular mechanisms leading to cancer. Advancements in genome‐wide methodologies and bioinformatic tools used for deciphering the consequences of altered DNA methylation patterns will enable deeper understanding of molecular mechanisms leading to the development of cancer.