title: Deregulated chromatin remodeling in the pathobiology of brain tumors.
abstract: Brain tumors encompass a heterogeneous group of malignant tumors with variable histopathology, aggressiveness, clinical outcome and prognosis. Current gene expression profiling studies indicate interplay of genetic and epigenetic alterations in their pathobiology. A central molecular event underlying epigenetics is the alteration of chromatin structure by post-translational modifications of DNA and histones as well as nucleosome repositioning. Dynamic remodeling of the fundamental nucleosomal structure of chromatin or covalent histone marks located in core histones regulate main cellular processes including DNA methylation, replication, DNA-damage repair as well as gene expression. Deregulation of these processes has been linked to tumor suppressor gene silencing, cancer initiation and progression. The reversible nature of deregulated chromatin structure by DNA methylation and histone deacetylation inhibitors, leading to re-expression of tumor suppressor genes, makes chromatin-remodeling pathways as promising therapeutic targets. In fact, a considerable number of these inhibitors are being tested today either alone or in combination with other agents or conventional treatments in the management of brain tumors with considerable success. In this review, we focus on the mechanisms underpinning deregulated chromatin remodeling in brain tumors, discuss their potential clinical implications and highlight the advances toward new therapeutic strategies.
authors.affiliation: Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, 11527, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Spyropoulou
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.forename: Christos
authors.initials: C
authors.lastname: Adamopoulos
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008745:Methylation / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009707:Nucleosomes / Q000502:physiology / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D009707:Nucleosomes; D000255:Adenosine Triphosphate; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases