The identification of cancer-associated mutations in the tricarboxylic acid (TCA) cycle
enzymes isocitrate dehydrogenases 1 and 2 (IDH1/2) highlights the prevailing notion that
aberrant metabolic function can contribute to carcinogenesis. IDH1/2 normally catalyse the
oxidative decarboxylation of isocitrate into α-ketoglutarate (αKG). In gliomas and acute
myeloid leukaemias, IDH1/2 mutations confer gain-of-function leading to production of the
oncometabolite R-2-hydroxyglutarate (2HG) from αKG. Here we show that generation of …