Differential and Common Signatures of miRNA Expression and Methylation in Childhood Central Nervous System Malignancies: An Experimental and Computational Approach

SIMPLE SUMMARY: Epigenetic mechanisms, that are modifications of the genome without the presence of mutations, are known to play a crucial role in central nervous system (CNS) tumors during childhood. Two well-known epigenetic regulatory mechanisms include methylation and miRNA regulatory mechanisms. Therefore, in the present study we have investigated the presence of methylated genes in childhood CNS tumors, along with miRNA expression. We have searched for correlations between gene methylation and miRNA expression. In addition, we have investigated mRNA expression in order to search for possible miRNA targets. Such approaches could prove useful for the improvement of CNS tumor prognosis, as well as for the discovery of new therapeutic targets. ABSTRACT: Epigenetic modifications are considered of utmost significance for tumor ontogenesis and progression. Especially, it has been found that miRNA expression, as well as DNA methylation plays a significant role in central nervous system tumors during childhood. A total of 49 resected brain tumors from children were used for further analysis. DNA methylation was identified with methylation-specific MLPA and, in particular, for the tumor suppressor genes CASP8, RASSF1, MGMT, MSH6, GATA5, ATM1, TP53, and CADM1. miRNAs were identified with microarray screening, as well as selected samples, were tested for their mRNA expression levels. CASP8, RASSF1 were the most frequently methylated genes in all tumor samples. Simultaneous methylation of genes manifested significant results with respect to tumor staging, tumor type, and the differentiation of tumor and control samples. There was no significant dependence observed with the methylation of one gene promoter, rather with the simultaneous presence of all detected methylated genes’ promoters. miRNA expression was found to be correlated to gene methylation. Epigenetic regulation appears to be of major importance in tumor progression and pathophysiology, making it an imperative field of study.