Glioma-derived mutations in IDH: from mechanism to potential therapy.
Heterozygous mutations in either the R132 residue of isocitrate dehydrogenase I (IDH1) or the R172 residue of IDH2 in human gliomas were recently highlighted. Heterozygous mutations in the IDH1 occur in the majority of grade II and grade III gliomas and secondary glioblastomas and change the structure of the enzyme, which diminishes its ability to convert isocitrate (ICT) to alpha-ketoglutarate (alpha-KG) and provides it with a newly acquired ability to convert alpha-KG to R(-)-2-hydroxyglutarate [R(-)-2HG]. The IDH1 and IDH2 mutations are relevant to the progression of gliomas, the prognosis and treatment of the patients with gliomas harboring the mutation. In this paper, we reviewed these recent findings which were essential for the further exploration of human glioma cancer and might be responsible for developing a newer and more effective therapeutic approach in clinical treatment of this cancer.
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, PR China. yjfu@sxu.edu.cn
Yuejun
Y
Fu
Rui
R
Huang
Jun
J
Du
Renjia
R
Yang
Na
N
An
Aihua
A
Liang
D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011487:Protein Conformation; D011836:Radiation Tolerance / Q000235:genetics
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007521:Isocitrate Dehydrogenase