MRS for D-2HG Detection in IDH-Mutant Glioma

Abstract

Recurrent heterozygous mutations of isocitrate dehydrogenase (IDH1 and IDH2) are primary genetic events in gliomagenesis and largely determine the subsequent evolution and clinical phenotype of this class of brain tumors. Mutations in the residues R132 of IDH1 or R172 of IDH2 switch the enzymatic activity towards the production of D-2-hydroxyglutarate (D-2HG) at high intracellular concentration. IDH1 and IDH2 are important hubs in the metabolic network and their mutations result in metabolic reprogramming of mutant glioma cells with far-reaching downstream effects such as epigenetic modifications and modulation of immune response that promote cancer. D-2HG has emerged as a versatile and multipurpose biomarker for gliomas to diagnose IDH mutations, for treatment planning, and to monitor response to standard chemoradiation or targeted therapies. Noninvasive imaging of D-2HG based on magnetic resonance spectroscopy is feasible in patients and may enable precision oncology in glioma patients. However, optimized MRS acquisitions for 2HG detection are necessary to reduce false positive and false negative results.