The most common modification that influences expression of genes is DNA methylation. Genes with highly methylated promoters typically are not well expressed. Changes from normal patterns of DNA methylation of specific genes can also cause alterations in gene expression that are associated with disease. 
Studies of DNA methylation are often coupled with gene expression studies and genetic variation studies, as DNA methylation can regulate gene expression [23]. And SNPs also modify DNA methylation[24,25]. Methylation of DNA involves the conversion of cytosine to methyl cytosine (5mC) by adding a methyl group at 5’ position at a site in DNA, and the oxidative intermediates generated during the de methylation processes(hydroxyl methyl, formyl, and carboxyl-cytosine) [26-28]. The cytosine nucleotide to be methylated is located next to a guanine nucleotide, i.e. in a CpGdinucleotide, although recent research has found methylated cytosine in other sequence contexts, such as CpA [26].
Epigenome-wide association studies (EWAS) hold promise for the detection of new regulatory mechanisms that may be susceptible to modification by environmental and lifestyle factors affecting disease[27]. Because of the rapid advances in sequencing technology, large numbers of methylated CpG sites can be identified across the entire genome. Studies of cancer frequently compare methylation sites in DNA from cancer tissues with sites in adjacent histologically tumor-free (i.e. normal) tissue. Both cancer and normal tissues are typically available because of surgical resection of the cancer surrounded by normal tissue margins. DNA methylation profiles have also been used as molecular tools to subgroup cancer patients for personalized treatment [28-30]. In addition, utilizing cell-free DNA methylation as diagnostic tools and markers for treatment efficacy, especially for early detection of cancer, are being rapidly developed [31-33]. However, not many studies have focused on childhood leukemia and brain tumors.