Science Times: 2-Hydroxy-Glutarate 3-Dimensional Functional Spectroscopy in the Evaluation of Isocitrate Dehydrogenase–Mutant Glioma Response to Therapy

Somatic mutations of the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2, respectively) are found in approximately 80% of World Health Organization (WHO) grade II/III gliomas and secondary glioblastomas (WHO grade IV).1 These mutations result in overreduction of α-ketoglutarate to the putative oncometabolite 2-hydroxy-glutarate (2HG). The accumulation of 2HG in cells is thought to play a key role in accelerating malignant transformation by promoting DNA hypermethylation, which in turn leads to genome-wide derangements in the epigenetic control of gene expression.2,3Because IDH-mutant gliomas have been found to have a favorable overall prognosis compared with wild-type tumors, the accumulation of 2HG in tumor cells has been studied as a predictive biomarker of IDH-mutant tumors.2,4 Noninvasive detection of 2HG with magnetic resonance spectroscopy (MRS) has gone through multiple phases. Although initial studies focused on the diagnostic and prognostic values of 2HG, a more recent study suggests that this molecule could be used for early identification of response to treatment.4 

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