%0 Journal Article
%T DNA Methylation, Histone Modifications, and Signal Transduction Pathways: A Close Relationship in Malignant Gliomas Pathophysiology
%A Ra¨²l Alel¨²-Paz
%A Nadia Ashour
%A Ana Gonz¨¢lez-Corpas
%A Santiago Ropero
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/956958
%X Gliomas are the most common type of primary brain tumor. Although tremendous progress has been achieved in the recent years in the diagnosis and treatment, its molecular etiology remains unknown. In this regard, epigenetics represents a new approach to study the mechanisms that control gene expression and function without changing the sequence of the genome. In the present paper we describe the main findings about the alterations of cell signaling pathways in the most aggressive glioma in the adult population, namely, glioblastoma, in which epigenetic mechanisms and the emerging role of cancer stem cell play a crucial function in the development of new biomarkers for its detection and prognosis and the corresponding development of new pharmacological strategies. 1. Introduction The majority of Central Nervous System (CNS) tumors have a glial origin. From a clinical point of view, gliomas can be classified into four grades on the basis of its histology and prognosis, encompassing three different tissue types: astrocytomas (about 70%), oligodendrogliomas (10¨C30%), and ependymomas (less than 10%). In this clinical scale, glioblastoma (GBM) corresponds to grade IV astrocytoma and represents the most aggressive glioma in the adult population, with a median overall survival between 9 and 12 months after the diagnosis, characterized by rapid growth and diffuse invasiveness into the adjacent brain parenchyma. 2. Epigenetic Mechanisms in Normal Cells Epigenetics can be defined as the study of mechanisms that control gene expression in a potentially heritable way [1]. In humans, the most widely studied epigenetic modification is the methylation of cytosine residues at the carbon 5 position (5£¿mC) within the CpG dinucleotides [2] mediated by DNA methyltransferases (DNMTs), a family of enzymes that catalyze the transfer of a methyl group from S-adenosyl methionine to the DNA. In mammals, there are three main DNMTs: DNMT1, DNMT3a, and DNMT3b. DNMT1 is the most abundant DNMT in the cell and is transcribed mostly during the S phase of the cell cycle [1]. Its activity is focused on the faithfully preservation of DNA methylation patterns, acting preferably on the hemimethylated DNA generated during semiconservative DNA replication. DNMT3a and-3b are thought to be responsible for establishing the pattern of methylation during embryonic development showing a high expression in embryonic stem cells and a downregulation in differentiated cells, although its function is not only restricted to the novo methylation; both contribute to the methylation of the sites missed by
%U http://www.hindawi.com/journals/jst/2012/956958/