Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

Nature

Volumn 462, Issue 7274, 2009, Pages 739-744

  Dang, Lenny ^a   White, David W ^a   Gross, Stefan ^a   Bennett, Bryson D ^b   Bittinger, Mark A ^a   Driggers, Edward M ^a   Fantin, Valeria R ^a   Jang, Hyun Gyung ^a   Jin, Shengfang ^a   Keenan, Marie C ^a   Marks, Kevin M ^a   Prins, Robert M ^c   Ward, Patrick S ^d   Yen, Katharine E ^a   Liau, Linda M ^c   Rabinowitz, Joshua D ^b   Cantley, Lewis C ^e   Thompson, Craig B ^d   Vander Heiden, Matthew G ^a,f   Su, Shinsan M ^a  

^a AGIOS PHARMACEUTICALS   (United States)

^b PRINCETON UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 HYDROXYGLUTARIC ACID; 2 OXOGLUTARIC ACID; ARGININE DERIVATIVE; HISTIDINE DERIVATIVE; ISOCITRATE DEHYDROGENASE; ISOCITRATE DEHYDROGENASE 1; ISOCITRIC ACID; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; UNCLASSIFIED DRUG;

AMINO ACID; BIOCHEMISTRY; CANCER; CATALYSIS; ENZYME ACTIVITY; METABOLISM; MUTATION;

AEROBIC METABOLISM; ARTICLE; CANCER GROWTH; CANCER RISK; CATALYSIS; DECARBOXYLATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME MECHANISM; GENE MUTATION; GLIOBLASTOMA; HUMAN; HUMAN CELL; IN VIVO STUDY; INBORN ERROR OF METABOLISM; METABOLITE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSAMINATION;

ARGININE; BRAIN NEOPLASMS; CATALYTIC DOMAIN; CELL LINE; CRYSTALLOGRAPHY, X-RAY; DISEASE PROGRESSION; ENZYME ASSAYS; GLIOMA; GLUTARATES; HISTIDINE; HUMANS; ISOCITRATE DEHYDROGENASE; KETOGLUTARIC ACIDS; MODELS, MOLECULAR; MUTANT PROTEINS; MUTATION; PROTEIN CONFORMATION;

EID: 72049125350     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature08617     Document Type: Article

References (26)

1. Balss, J. et al. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol. 116, 597-602 (2008).
2. Watanabe, T., Nobusawa, S., Kleihues, P. & Ohgaki, H. IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am. J. Pathol. 174, 1149-1153 (2009).
3. Yan, H. et al. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360, 765-773 (2009).
4. Hartmann, C. et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol. 118, 469-474 (2009).
5. Parsons, D. W. et al. An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807-1812 (2008).
6. Bleeker, F. E. etal. IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum. Mutat. 30, 7-11 (2009).
7. Zhao, S. et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1a. Science 324, 261-265 (2009).
8. Lu, W., Kimball, E. & Rabinowitz, J. D. A high-performance liquid chromatography-tandem mass spectrometry method for quantitation of nitrogen-containing intracellular metabolites. J. Am. Soc. Mass Spectrom. 17, 37-50 (2006).
9. Struys, E. A., Jansen, E. E., Verhoeven, N. M. & Jakobs, C. Measurement of urinary D-and L-2-hydroxyglutarate enantiomers by stable-isotope-dilution liquid chromatography-tandem mass spectrometry after derivatization with diacetyl-L-tartaric anhydride. Clin. Chem. 50, 1391-1395 (2004).
10. Xu, X. et al. Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity. J. Biol. Chem. 279, 33946-33957 (2004).
11. Aktas, D. F. & Cook, P. F. A lysine-tyrosine pair carries out acid-base chemistry in the metal ion-dependent pyridine dinucleotide-linked b-hydroxyacid oxidative decarboxylases. Biochemistry 48, 3565-3577 (2009).
12. Struys, E. A. et al. Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Am. J. Hum. Genet. 76, 358-360 (2005).
13. Kölker, S., Mayatepek, E. & Hoffmann, G. F. White matter disease in cerebral organic acid disorders: clinical implications and suggested pathomechanisms. Neuropediatrics 33, 225-231 (2002).
14. Wajner, M., Latini, A., Wyse, A. T. & Dutra-Filho, C. S. The role of oxidative damage in the neuropathology of organic acidurias: insights from animal studies. J. Inherit. Metab. Dis. 27, 427-448 (2004).
15. Aghili, M., Zahedi, F. & Rafiee, E. Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review. J. Neurooncol. 91, 233-236 (2009).
16. Kolker, S. et al. NMDA receptor activation and respiratory chain complex V inhibition contribute to neurodegeneration in D-2-hydroxyglutaric aciduria. Eur. J. Neurosci. 16, 21-28 (2002).
17. Latini, A. et al. D-2-hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats. Eur. J. Neurosci. 17, 2017-2022 (2003).
18. Tsacopoulos, M. Metabolic signaling between neurons and glial cells: a short review. J. Physiol. (Paris) 96, 283-288 (2002).
19. Mardis, E. R. et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 361, 1058-1066 (2009).
20. Luo, B., Groenke, K., Takors, R., Wandrey, C. & Oldiges, M. Simultaneous determination of multiple intracellular metabolites in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle by liquid chromatography-mass spectrometry. J. Chromatogr. A 1147, 153-164 (2007).
21. Munger, J. et al. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nature Biotechnol. 26, 1179-1186 (2008).
22. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode (HKL2000). Methods Enzymol. 276, 307-326 (1997).
23. McCoy, A. J. et al. Phaser Crystallographic Software. J. Appl. Cryst. 40, 658-674 (2007).
24. Emsley, P. & Cowtan, K. COOT: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126-2132 (2004).
25. Collaborative Computational Project, Number 4. The CCP4 Suite: Programs for Protein Crystallography. Acta Crystallogr. D 50, 760-763 (1994).
26. DeLano, W. L. The PyMOL Molecular Graphics System (DeLano Scientific, 2002).