Neuroblastoma starts in early forms of nerve cells found in a developing embryo or fetus. About 6% of childhood cancers are neuroblastomas. This type of cancer develops in infants and young children. It is rarely found in children older than 10. The tumor can start anywhere but usually starts in the belly (abdomen) where it is noticed as swelling. It can also cause bone pain and fever.
DNA methylation in pediatric cancers
DNA methylation mechanism
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 methyl- ate 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).