DNA methylation in pediatric cancers
DNA methylation mechanism
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066610/pdf/2021.pdf
Cytosine methylation is carried out by a family of DNA methyltransferases, including DNMT1, DNMT3A, and DNMT3B (Okano et al. 1998). DNMT1 is considered as the maintenance DNA methyltransferase that can bind hemimethylated DNA during cell division, result- ing in the inheritance of the methylated cytosine state in the daughter strand. DNMT3A and DNMT3B function as de novo DNA methyltransferases, which can methylate the unmethylated cytosines during embryogenesis (Fig. 4A; Stein et al. 1982; Okano et al. 1998; Jones and Liang 2009).
DNA methylation was long considered to be an irre-versible epigenetic modification that could be removed only by the passive mechanism of cell division. This view was reversed by the discovery of the TET (ten-elev- en translocation) family of dioxygenases that use oxygen, Fe(II), and a-ketoglutarate as substrates in a sequential enzymatic reaction to convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and subsequently into 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) (Iyer et al. 2009; Tahiliani et al. 2009). In the active demethylation pathway,5mC is successively oxidized by members of theTET family to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- carboxylcytosine (5caC). 
From: Epigenetic changes in pediatric solid tumors: promising new targets
More recent studies have identified DNA demethylases (TET1,2) which hydroxylate 5-Methylcytosine(5mC) in CpG dinucleotides to 5- Hydroxymethylcytosine(5-hC). Evidence proposes that TET enzymes are capable of iterative oxidation on substrates to 5-formylmethylcytosine (5-fC) or 5- carboxymethylcytosine(5-caC) (23, 24). This leads to substrates upon which base excision repair mechanisms mediated by thymine-DNA glycosylase (TDG) excise a modified C and replace with an unmodified C, allowing for rapid re-activation (gene ON) of previously silenced genes (24).
http://cancerres.aacrjournals.org/content/78/13_Supplement/2270
Epigenetic mechanisms, such as 5-methylcytosine (5mC), are known to play a major role in breast cancer. However, the role of 5-hydroxymethylcytosine (5hmC) DNA modification remains understudied. We hypothesize that 5hmC mediates redox regulation of gene expression in the triple negative breast cancer (TNBC) subtype. To address this, our objective was to highlight genes that may be the target of this process by identifying redox-regulated, antioxidant-sensitive, gene-localized 5hmC changes associated with mRNA changes in TNBC cells. We proceeded to develop an approach to integrate data sets generated by a methodology called Pvu-sequencing, which measures 5hmC in the genome, and RNA-sequencing. The result of our approach to merge genome-wide, high-throughput TNBC cell line data to identify significant, concordant 5hmC and mRNA changes in response to antioxidant treatment, that perturbs redox signaling, produced a gene set with relevance to alternative mRNA splicing and cancer stem cell function.
http://tcr.amegroups.com/article/view/4482/html
Above link Very imp. for general overview of DNA methylation 
5-hydroxymethylation (5-hmC) was first described as a product of 5-mC oxidation by TET1 (ten-eleven translocase) [reviewed in (14,15)]. Two additional TET enzymes, TET2 and TET3, were subsequently identified, with each TET enzyme functioning as 2-oxoglutarate- and iron-dependent dioxygenases that are similar in function to several known histone lysine demethylases. TET enzymes can catalyze the conversion of 5-mC to not only 5-hmC, but also the subsequent conversion of 5-hmC to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC). The latter (5-fC and 5-caC) are substrates for thymine DNA glycosylase-mediated base excision repair that results with replacement of the 5-fC and 5-caC base by an unmethylated cytosine. 5-hmC is present at lower levels (<1%) than 5-mC (4-5%), but 5-hmC marks are found at gene promoters, gene bodies and enhancers across tissue types. Specifically, the highest 5-hmC levels are found in brain, colorectal, kidney and liver tissues, whereas 5-hmC levels are substantially lower in heart and breast tissues (16). 5-hmC profiles are also altered in several human cancers [reviewed in (17)], and represent an important step in enzyme-catalyzed DNA demethylation, as well as potential cancer-specific biomarkers (18-22).