DNA methylation of cancer genome

Abstract

DNA methylation plays an important role in regulating normal development and carcinogenesis. Current understanding of the biological roles of DNA methylation is limited to its role in the regulation of gene transcription, genomic imprinting, genomic stability, and X chromosome inactivation. In the past 2 decades, a large number of changes have been identified in cancer epigenomes when compared with normals. These alterations fall into two main categories, namely, hypermethylation of tumor suppressor genes and hypomethylation of oncogenes or heterochromatin, respectively. Aberrant methylation of genes controlling the cell cycle, proliferation, apoptosis, metastasis, drug resistance, and intracellular signaling has been identified in multiple cancer types. Recent advancements in whole-genome analysis of methylome have yielded numerous differentially methylated regions, the functions of which are largely unknown. With the development of high resolution tiling microarrays and high throughput DNA sequencing, more cancer methylomes will be profiled, facilitating the identification of new candidate genes or ncRNAs that are related to oncogenesis, new prognostic markers, and the discovery of new target genes for cancer therapy. †

DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

“…[8][9][10][11] This specific derepression of protooncogenes may lead to overcome the apoptotic pathways and generate survival of transformed neoplastic cells. 34 In our data, the induced networks and several individual CpG sites, annotated to specific genes, suggest a mechanism related to tumor suppressor release (RB1), or oncogene activation (SOX2), which may explain part of the THM mechanism in humans. Moreover, some of the differentially methylated sites and regions are located in genes related to both or, specifically, to either bladder cancer 16,20 or colorectal cancer 21,35 (MYNN, SOX2, RB1, and SMAD3), which supports this hypothesis.…”

DNA methylation in germ cell tumour aetiology: current understanding and outstanding questions

“…This is attributed to a loss of methylation in intergenic regions containing repetitive elements and is associated with chromosomal instability and activation of endogenous mobile DNA elements (Esteller 2007, Portela & Esteller 2010. On the other hand, hypermethylation of gene promoter regions is also seen in almost all cancer types with many reports of tumour suppressor genes being silenced (Cheung et al 2009, Dawson & Kouzarides 2012. Silencing of some genes, such as RASSF1A, CDKN2A/p16 and MGMT, by promoter hypermethylation is especially common and is seen across many cancer types whereas methylation of other genes is much more cancer type specific (Esteller 2007, Cheung et al 2009).…”

“…On the other hand, hypermethylation of gene promoter regions is also seen in almost all cancer types with many reports of tumour suppressor genes being silenced (Cheung et al 2009, Dawson & Kouzarides 2012. Silencing of some genes, such as RASSF1A, CDKN2A/p16 and MGMT, by promoter hypermethylation is especially common and is seen across many cancer types whereas methylation of other genes is much more cancer type specific (Esteller 2007, Cheung et al 2009). …”

“…Abnormal DNMT activity has been associated with methylator phenotypes such as those seen in colorectal and breast cancers as well as GCTs (see below) (Roll et al 2008, Cheung et al 2009, Karpinski et al 2010. The only DNMT gene in which mutations have been described in relation to cancer is DNMT3A.…”

“…Aberrant epigenetic changes are widely believed to participate in cancer development (Cheung et al 2009). In GCTs, DNA methylation is especially interesting as the methylation status of the genome is in flux during the normal development of germ cells.…”