Biological And Most Aggressive Type Of Brain Malignancy

Recent studies including a genome-wide study of certain cancers have come to demonstrate that the most common and most aggressive type of brain malignancy, or glioblastoma (GBM) comprises a shared link: alterations in the catalytic protein, isocitrate dehydrogenase (IDH) (1). The focus of such research is the mutant forms of NADP-dependent homologous enzymes IDH1 and IDH2 (2) - localized predominantly in cytosolic and mitochondrial regions, respectively. Both of these heterozygous point mutations modify the amino acid residue present at the active site of the original enzyme. Subsequently, neomorphic activity of the enzyme IDH is established, replacing its original function with the conversion of the ÃŽ ±-Ketoglutarate (ÃŽ ±-KG) to D-2-hydroxyglutarate (D-2-HG), an oncogenic metabolite (3). The presence of IDH1/2 mutants in cells is consistent with abnormally high levels of this tumor progressor, D-2-HG, which inhibits catalytic proteins that are ÃŽ ±-KG-dependent (4). As a result, D -2-HG indirectly influences epigenetic regulation, the formation of collagen as well as histone methylation. Transgenic mouse models are now advancing to provide insight into the effects of IDH mutations in tandem with other cooperating mutations better understand glioma pathogenesis (5). The biochemical pathways involved in IDH mutant forms (IDH1m, IDH2m) reveal that a substitution of the arginine residue 132 with histidine is responsible for the pathogenic changes due to IDH1 mutations (6) (Figure 1).Show MoreRelatedCancer Is Defined By The National Cancer Institute2215 Words   |  9 PagesCancer is defined by the National Cancer Institute as â€Å"the name given to a collection of related diseases. 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