Abstract
Simple SummaryEpigenetic 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.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.
Highlights
Cancer is one of the leading fatal diseases in the western world
We have analyzed a cohort of pediatric patients suffering from different types of central nervous system (CNS) tumors, including ependymoma, medulloblastoma, atypical teratoid/rhabdoid tumors (ATRT), and astrocytoma
For part of the patient cohort, the information concerning the time of death was not known and, it was not possible to calculate the overall survival for all patients
Summary
Tumors of the central nervous system (CNS), are considered to be a complex, heterogeneous disease that is often fatal. Scientific knowledge gained through intense research, have not yet been translated into similar improvements in tumor patients. CNS tumors still remain a critical health condition, challenging both the patient as well as the health professionals. CNS tumors are a pathological condition of unknown etiology that lead to the formation of solid mass growing uncontrollably. They are characterized by abnormalities and disorders in the proliferation, differentiation, and gene expression of a particular cell population, which usually results in abnormal cell function. The etiology of CNS tumors is not fully understood, there are specific factors that increase the risk of developing the disease
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