title: IDH mutations associated impact on related cancer epidemiology and subsequent effect toward HIF-1α.
abstract: Particular mutations in the isocitrate dehydrogenase gene (IDH) were discovered in several gliomas citing astrocytoma, oligodendroglioma, and glioblastoma multiform, but also in leukemia; these mutations were discovered in nearly all cases of secondary glioblastomas, they evolve from lower-grade gliomas, but are limited in primary high-grade glioblastoma multiform. These mutations distinctively produce (D)-2-hydroxyglutarate (D-2-HG) from alpha-ketoglutarate (α-KG). (D)-2-hydroxyglutarate is accumulated to very high concentrations which inhibit the function of enzymes that are dependent on alpha-ketoglutarate. This modification leads to a hyper-methylated state of DNA and histones, resulting in different gene expression that can activate oncogenes and inactivate tumor-suppressor genes. In our work we review the impact of the mutations that occur in IDH genes, we focus on their impact on distribution in cancer. As IDH mutations appear in many different conditions we expose the extent of IDH mutations and derivate their impact on cancer prognosis, diagnosis, and even their oncogenicity, we will also link their impact to HIF-1α and derivate some target and finally, we present some of the therapeutics under research and out on market.
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Herve
authors.initials: H
authors.lastname: Semukunzi
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Debmalya
authors.initials: D
authors.lastname: Roy
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ghulam Jilany
authors.initials: GJ
authors.lastname: Khan
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Lyu
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: Yuanst@cpu.edu.cn.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 1020081892@cpu.edu.cn.
authors.forename: Sensen
authors.initials: S
authors.lastname: Lin
mesh_terms: D015415:Biomarkers; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007521:Isocitrate Dehydrogenase
keywords: (D)-2-hydroxyglutarate (D-2-HG); Epidemiology; Hypoxia inducible factor (HIF); Isocitrate dehydrogenase (IDH); Oncogenicity