DNA methylation and cancer

Abstract

The methylation of DNA is an epigenetic modification that can play an important role in the control of gene expression in mammalian cells. The enzyme involved in this process is DNA methyltransferase, which catalyzes the transfer of a methyl group from S-adenosyl-methionine to cytosine residues to form 5-methylcytosine, a modified base that is found mostly at CpG sites in the genome. The presence of methylated CpG islands in the promoter region of genes can suppress their expression. This process may be due to the presence of 5-methylcytosine that apparently interferes with the binding of transcription factors or other DNA-binding proteins to block transcription. In different types of tumors, aberrant or accidental methylation of CpG islands in the promoter region has been observed for many cancer-related genes resulting in the silencing of their expression. How this aberrant hypermethylation takes place is not known. The genes involved include tumor suppressor genes, genes that suppress metastasis and angiogenesis, and genes that repair DNA suggesting that epigenetics plays an important role in tumorigenesis. The potent and specific inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-AZA-CdR) has been demonstrated to reactivate the expression most of these "malignancy" suppressor genes in human tumor cell lines. These genes may be interesting targets for chemotherapy with inhibitors of DNA methylation in patients with cancer and this may help clarify the importance of this epigenetic mechanism in tumorigenesis.

Methylation analysis of the glypican 3 gene in embryonal tumours

“…These observations might result from the fact that cancer cells often present aberrant methylation, their genome being generally hypomethylated and locally hypermethylated, notably in CpG islands (Baylin et al, 1998;Momparler and Bovenzi, 2000;Robertson and Jones, 2000). Our study suggests that the main methylation abnormalities at the GPC3 promoter level seems to be losses of methylation in NBs and the opposite in WTs.…”

Aberrant DNA Methylation of P16, MGMT, hMLH1 and hMSH2 Genes in Combination with the MTHFR C677T Genetic Polymorphism in Gastric Cancer

“…Previous study indicated aberrant methylation of DNA plays an important role in epigenetic changes and occurrence of various cancers (Momparler and Bovenzi, 2000). Lack of global DNA methylation may cause the instability of gene, and thus promote the process of cancer development (Sato and Meltzer, 2006).…”

Epigenetic landscape and miRNA involvement during neural crest development

“…It has been well established in cancer and stem cells that high CpG methylation occurs at the promoter region correlates with inhibition of gene expression (Momparler and Bovenzi, 2000;Miranda and Jones, 2007;Altun et al, 2010). Moreover, there are several studies that highlight the importance of DNA methylation in disease and during normal development of organisms (Martin et al, 1999;Mhanni and McGowan, 2004;Linhart et al, 2007;Ehrlich et al, 2008).…”