Molecular Diagnostics of Brain Tumours by Measuring the 5-Methylcytosine Level in Their DNA

Brain tumours form a group of neoplasms with distinct histological characteristics and different malignancies [Maher 2001]. Various molecular alterations occurring in brain tumors may have diagnostic and predictive values as they are connected with histologically determined tumour types and malignancy grades [Martinez et al. 2009; Martinez and Esteller 2010; Sciume et al. 2010]. Methylation of DNA cytosine residue at the carbon 5 position (m5C) is a common epigenetic marker in many eukaryotes and is often found in the sequence context of CpG. It is assumed that ca 5% of all cytosine residues, i.e. 1% of the nucleic bases, in mammalian genomes are methylated. Although DNA methylation has been viewed as a stable epigenetic mark, studies in the past decade have revealed that this modification is not as static [Wu and Zhang 2010]. In fact, loss of DNA methylation (DNA hypomethylation), has been observed in the specific context and can occur through active, passive or random modification mechanisms. Although the genome in each cell within the body is identical, celland tissue-specific profiles of gene transcription, posttranscriptional modification, modifications and translation are specifically regulated by epigenetic mechanisms that include DNA methylation, histone modification and noncoding RNAs [Robertson 2005]. In the central nervous system epigenetic mechanisms serve as main regulators of homeostasis and plasticity development, which are sensitive to local and global environmental, vascular and systemic factors [Martinez and Esteller 2010]. It is generally accepted that cancer initiation and progression are linked to the disruption of red-ox balance of the cell [Grek and Tew 2010]. Current evidences support an idea that cancer cells are generated by enhanced reactive oxygen species (ROS) generation, their accumulation, and down regulation of antioxidant enzymes [Essick and Sam 2010]. The oxidative damage to the cell caused by ROS plays a critical role in the etiology and progression of different neoplasms in humans [Johnstone and Baylin 2010; Jomova and Valko 2011]. Oxygen radicals cause damage to DNA and chromosomes, induce epigenetic alterations, interact with oncogenes or tumour suppressor genes, and finally change the immunological mechanisms [Robertson 2005; Pelizzola and Ecker 2010].