Epigenetic mechanisms in glioblastoma multiforme

• Published in: Seminars in cancer biology Vol. 19; no. 3; pp. 188 - 197
• Main Authors: Nagarajan, Raman P., Costello, Joseph F.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2009
• Subjects: Biomarkers, Tumor - metabolism; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - genetics; Central Nervous System Neoplasms - metabolism; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA Methylation; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; Enzyme Inhibitors - therapeutic use; Epigenesis, Genetic - drug effects; Epigenetics; Gene Expression Regulation, Neoplastic; Gene Silencing - physiology; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - metabolism; Hematology, Oncology and Palliative Medicine; Histone Deacetylases - metabolism; Histones - metabolism; Humans; MicroRNAs - metabolism; Polycomb-Group Proteins; Promoter Regions, Genetic; Repressor Proteins - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; SAHA; TSA; CGI; MGMT; LOI; Glioblastoma; ICF; TIC; 5-aza; DNMT; GBM; Epigenetics; DNA methylation; HDACi; HDAC; glioblastoma multiforme; trichostatin A; suberoylanilide hydroxamic acid; loss of imprinting; immunodeficiency, centromere instability and facial anomalies; CpG island; O6-methylguanine-DNA methyltransferase; histone deacetylase inhibitor; tumor initiating cell; histone deacetylase; DNA methyltransferase; 5-aza-2′-deoxycytidine
• ISSN: 1044-579X; 1096-3650; 1096-3650
• DOI: 10.1016/j.semcancer.2009.02.005

Glioblastoma multiforme (GBM) is an aggressive and lethal cancer, accounting for the majority of primary brain tumors in adults. GBMs are characterized by genetic alterations large and small, affecting genes that control cell growth, apoptosis, angiogenesis, and invasion. Epigenetic alterations also affect the expression of cancer genes alone, or in combination with genetic mechanisms. For example, in each GBM, hundreds of genes are subject to DNA hypermethylation at their CpG island promoters. A subset of GBMs is also characterized by locus-specific and genome-wide decrease in DNA methylation, or DNA hypomethylation. Other epigenetic alterations, such as changes in the position of histone variants and changes in histone modifications are also likely important in the molecular pathology of GBM, but somewhat surprisingly there are very limited data about these in GBM. Alterations in histone modifications are especially important to understand, given that histone deacetylases are targets for drugs that are in clinical trial for GBMs. The technological wave of next-generation sequencing will accelerate GBM epigenome profiling, allowing the direct integration of DNA methylation, histone modification and gene expression profiles. Ultimately, genomic and epigenomic data should provide new predictive markers of response and lead to more effective therapies for GBM.