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Glioma-derived mutations in isocitrate dehydrogenase 2 beneficial to traditional chemotherapy.

Authors: Fu, Y  Huang, R  Zheng, Y  Zhang, Z  Liang, A 
Citation: Fu Y, etal., Biochem Biophys Res Commun. 2011 Jul 1;410(2):218-23. doi: 10.1016/j.bbrc.2011.05.108. Epub 2011 May 27.
Pubmed: (View Article at PubMed) PMID:21641335
DOI: Full-text: DOI:10.1016/j.bbrc.2011.05.108

Heterozygous mutations in either the R132 residue of isocitrate dehydrogenase I (IDH1) or the R172 residue of IDH2 in human gliomas were recently highlighted. In the present study, we report that mutations of IDH1 and IDH2 are not detected in the rat C6 glioma cell line model, which suggests that these mutations are not required for the development of glioblastoma induced by N,N'-nitroso-methylurea. The effects of IDH2 and IDH2(R172G) on C6 cells proliferation and sensitivity to chemotherapy and the possible mechanism are analyzed at the cellular level. IDH1 and IDH2 mutations lead to simultaneous loss and gain of activities in the production of alpha-ketoglutarate (alpha-KG) and 2-hydroxyglutarate (2HG), respectively, and result in lowering NADPH levels even further. The low NADPH levels can sensitize tumors to chemotherapy, and account for the prolonged survival of patients harboring the mutations. Our data extrapolate potential importance of the in vitro rat C6 glioma cell model, show that the IDH2(R172G) mutation in gliomas may give a benefit to traditional chemotherapy of this cancer and serve as an important complement to existing research on this topic.

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CRRD Object Information
CRRD ID: 11522736
Created: 2016-08-05
Species: All species
Last Modified: 2016-08-05
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.