Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

L Dang, DW White, S Gross, BD Bennett, MA Bittinger… - Nature, 2009 - nature.com
mutated in tumours, raising the possibility that the mutations do not result in a simple loss
of function. Here we show that cancer-associated IDH1 mutations … (-)-2-hydroxyglutarate (2HG). …

Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia

ZJ Reitman, CG Duncan, E Poteet, A Winters… - Journal of Biological …, 2014 - ASBMB
… However, the effect of the cancer-associated IDH1 mutations on reductive glutamine metabolism
has not been fully explored. Alterations in the steady-state levels of metabolites derived …

2-Hydroxyglutarate in cancer cells

P Ježek - Antioxidants & redox signaling, 2020 - liebertpub.com
… ) R140Q provide cells with millimolar r-2-hydroxyglutarate (r-2HG) concentrations, whereas
… form submillimolar s-2-hydroxyglutarate (s-2HG). However, even wild-type IDH1 and IDH2, …

Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations

S Gross, RA Cairns, MD Minden, EM Driggers… - Journal of Experimental …, 2010 - rupress.org
IDH1 mutations cause a gain-of-function, resulting in the production and accumulation of
2-hydroxyglutarate (… Genotyping of 145 AML biopsies identified 11 IDH1 R132 mutant samples. …

Cancer-associated mutation and beyond: The emerging biology of isocitrate dehydrogenases in human disease

S Tommasini-Ghelfi, K Murnan, FM Kouri… - Science …, 2019 - science.org
… and energy production through generation of NADH. Cancer-associated mutations in
IDH1 and … Mutant enzymes produce (R)-2-hydroxyglutarate, which in turn inhibits αKG-dependent …

The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate

PS Ward, J Patel, DR Wise, O Abdel-Wahab… - Cancer cell, 2010 - cell.com
… It has been recently reported that cancer-associated IDH1 R132 mutants display a loss-of-function
for the use of isocitrate as substrate, with a concomitant gain-of-function for the …

[HTML][HTML] Characterization of cancer-associated IDH2 mutations that differ in tumorigenicity, chemosensitivity and 2-hydroxyglutarate production

KP Kotredes, R Razmpour, E Lutton, M Alfonso-Prieto… - Oncotarget, 2019 - ncbi.nlm.nih.gov
… different mutants of IDH1 (R132H, R132C, and R132G) [53] show that the IDH1 mutants
indeed have a differential production of (R)-2-HG, similar to our results with the IDH2 mutants. …

Identification of additional IDH mutations associated with oncometabolite R (−)-2-hydroxyglutarate production

PS Ward, JR Cross, C Lu, O Weigert, O Abel-Wahab… - Oncogene, 2012 - nature.com
… However, on the basis of this study there are at least five reproducible cancer-associated
mutations that can result in 2HG production and these appear to be selected for in several well-…

Cancer-associated IDH mutations: biomarker and therapeutic opportunities

KE Yen, MA Bittinger, SM Su, VR Fantin - Oncogene, 2010 - nature.com
Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous
leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 207: 339–344. …

Evidence that 2-hydroxyglutarate is not readily metabolized in colorectal carcinoma cells

SJ Gelman, NG Mahieu, K Cho, EM Llufrio… - Cancer & …, 2015 - Springer
IDH1 mutation has a metabolic effect in these cells. We hypothesized that the altered features
in IDH1 mutant … might be increased in the IDH1 mutant dataset from the current experiment. …