The DNA methylation landscape in cancer

Abstract

As one of the most abundant and well-studied epigenetic modifications, DNA methylation plays an essential role in normal development and cellular biology. Global alterations to the DNA methylation landscape contribute to alterations in the transcriptome and deregulation of cellular pathways. Indeed, improved methods to study DNA methylation patterning and dynamics at base pair resolution and across individual DNA molecules on a genome-wide scale has highlighted the scope of change to the DNA methylation landscape in disease states, particularly during tumorigenesis. More recently has been the development of DNA hydroxymethylation profiling techniques, which allows differentiation between 5mC and 5hmC profiles and provides further insights into DNA methylation dynamics and remodeling in tumorigenesis. In this review, we describe the distribution of DNA methylation and DNA hydroxymethylation in different genomic contexts, first in normal cells, and how this is altered in cancer. Finally, we discuss DNA methylation profiling technologies and the most recent advances in single-cell methods, bisulfite-free approaches and ultra-long read sequencing techniques.

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

“…DNA 5-methylcytosine (m 5 C) has been found to be the most abundant DNA modification in mammalian cells and is characterized by the addition of a methyl group at the carbon-5 position of the cytosine base [ 3 ]. In eukaryotes, the role of m 5 C in DNA and its oxidized derivatives, including 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), has been extensively studied (reviewed in [ 4 ]). In recent years, great progress has been made in the research of RNA modifications, which were originally regarded as fine-tuning chemostructural features of non-protein-coding RNAs but are now considered to be dynamically regulated, reversible and widespread posttranscriptional regulators in diverse cellular processes (reviewed in [ 5 ]).…”

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

“…As a critical type of epigenetic modification, genome methylation, including 5-methylcytosine (5mC), N6methyladenosine (m6A), and N1-methyladenosine (m1A), has gained increasing attention recently (Roundtree et al, 2017). In mammalian cells, DNA methylation is accomplished by DNA methyltransferase enzymes, which add a methyl group at carbon-5 of the cytosine bases (Skvortsova et al, 2019), thus repressing transcription in the genome. The frequency and number of aberrant DNA methylations are thought to be closely correlated with HCC (Nishida et al, 2008).…”

Global DNA (hydroxy)methylation is stable over time under several storage conditions and temperatures

“…DNA methylation can be actively de-methylated through the oxidation by Ten-eleven-Translocation (TET) enzymes to 5-hydroxymethylcytosine (5hmC) which can also act as an epigenetic modifier itself [3,4]. DNA methylation and hydroxymethylation have previously been associated with several diseases like cancer, heart disease, autoimmune diseases, and neurological disorders [5][6][7][8][9][10], and are therefore potential biomarkers for disease onset, progression, or response to medication [11]. DNA is required for epigenetic studies, which is mainly extracted from blood samples that have been collected from patients over several years and has therefore been stored for different time periods prior to the start of a study.…”