The DNA methylation landscape in cancer

Skvortsova, Ksenia; Stirzaker, Clare; Taberlay, Phillippa C.

doi:10.1042/ebc20190037

Cited by 209 publications

(178 citation statements)

References 146 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…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 ]).…”

Section: Introductionmentioning

confidence: 99%

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

Xue

Zhao

2020

Biomark Res

View full text Add to dashboard Cite

As an important posttranscriptional modification of RNA, 5-methylcytosine (m5C) has attracted increasing interest recently, with accumulating evidence suggesting the involvement of RNA m5C modification in multiple cellular processes as well as tumorigenesis. Cooperatively, advances in m5C detection techniques have enabled transcriptome mapping of RNA methylation at single-nucleotide resolution, thus stimulating m5C-based investigations. In this review, we summarize currently available approaches for detecting m5C distribution in RNA as well as the advantages and disadvantages of these techniques. Moreover, we elucidate the regulatory mechanisms of RNA m5C modification by introducing the molecular structure, catalytic substrates, cellular distributions and biological functions of RNA m5C regulators. The functional consequences of m5C modification on mRNAs, tRNAs, rRNAs and other RNA species, including viral RNAs and vault RNAs, are also discussed. Finally, we review the role of RNA m5C modification in cancer pathogenesis and progression, in hopes of providing new insights into cancer treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Xue

Zhao

2020

Biomark Res

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Cao

Luo

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

Background: 5-methylcytosine (5mC) has been reported in the prognosis of a variety of cancers, however, its role in hepatocellular carcinoma (HCC) has not been investigated yet. This study aimed at identifying the molecular subtypes associated with 5mC and establishing a relevant score to predict its prognosis in HCC. Methods: Somatic gene mutation data and gene expression data were retrieved from The Cancer Genome Atlas database. Molecular subtypes were identified by unsupervised clustering based on the expression of 5mC regulators, and the molecular features of each subtype were investigated by survival, mutation, gene set variation, and immune cell infiltration analyses. Next, we performed a differentially expressed analysis based on the new subtypes and selected the overlapping genes for further analysis. We undertook univariate Cox analysis to analyze these genes and constructed a prognostic model by lasso regression analysis. Meanwhile, survival and gene set enrichment analyses were used to explore the prognosis and the relevant pathways, respectively. The LIRI cohort from the International Cancer Genome Consortium database was used as a reference to validate the 5mC subtypes and 5mC score. Results: Twenty-one types of 5mC regulators were employed in this study, and three 5mC-associated molecular subtypes were identified. These three subtypes presented significant differences in prognosis, immune cell infiltration, immune checkpoint inhibitors, signaling pathways, and mutational features. Compared with cluster 3, cluster 2 exhibited significantly increased expression of PD-L1, TIM3, Galectin9, CTLA4, and CD80, while PD-L1, TIM3, and CD80 were higher in cluster 2 than in cluster 1. Furthermore, a 5mC-related score, composed of seven genes (SGPP2, SALL4, B3GNT7, ROR1, MYBL2, SLC7A1, and CAND2), was proven to be significantly associated with prognosis. The established subtypes and scores were thus successfully verified by the validated cohort.

show abstract

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

Background: Epigenetic markers are often quantified and related to disease in stored samples. While, effects of storage on stability of these markers have not been thoroughly examined. In this longitudinal study, we investigated the influence of storage time, material, temperature, and freeze-thaw cycles on stability of global DNA (hydroxy)methylation. Methods: EDTA blood was collected from 90 individuals. Blood (n = 30, group 1) and extracted DNA (n = 30, group 2) were stored at 4°C, −20°C and −80°C for 0, 1 (endpoint blood 4°C), 6, 12 or 18 months. Additionally, freeze-thaw cycles of blood and DNA samples (n = 30, group 3) were performed over three days. Global DNA methylation and hydroxymethylation (mean ± SD) were quantified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) with between-run precision of 2.8% (methylation) and 6.3% (hydroxymethylation). Effects on stability were assessed using linear mixed models. Results: global DNA methylation was stable over 18 months in blood at −20°C and −80°C and DNA at 4°C and −80°C. However, at 18 months DNA methylation from DNA stored at −20°C relatively decreased −6.1% compared to baseline. Global DNA hydroxymethylation was more stable in DNA samples compared to blood, independent of temperature (p = 0.0131). Stability of global DNA methylation and hydroxymethylation was not affected up to three freeze-thaw cycles. Conclusion: Global DNA methylation and hydroxymethylation stored as blood and DNA can be used for epigenetic studies. The relevance of small differences occuring during storage depend on the expected effect size and research question.

show abstract

The DNA methylation landscape in cancer

Cited by 209 publications

References 146 publications

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

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

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

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

Contact Info

Product

Resources

About