Many patients with
glioma harbor specific mutations in the
isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated
tumors produce the oncometabolite
2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to
lipid synthesis, we hypothesized that IDH1-mutant
tumors have an altered
phospholipid metabolite profile that would impinge on
tumor pathobiology. To investigate this hypothesis, we performed (31)P-MRS imaging in mouse xenograft models of four human
gliomas, one of which harbored the IDH1-R132H mutation. (31)P-MR spectra from the IDH1-mutant
tumor displayed a pattern distinct from that of the three IDH1 wild-type
tumors, characterized by decreased levels of
phosphoethanolamine and increased levels of glycerophosphocholine. This spectral profile was confirmed by ex vivo analysis of
tumor extracts, and it was also observed in human surgical biopsies of IDH1-mutated
tumors by (31)P high-resolution magic angle spinning spectroscopy. The specificity of this profile for the IDH1-R132H mutation was established by in vitro (31)P-NMR of extracts of cells overexpressing IDH1 or IDH1-R132H. Overall, our results provide evidence that the IDH1-R132H mutation alters
phospholipid metabolism in
gliomas involving
phosphoethanolamine and glycerophosphocholine. These new noninvasive
biomarkers can assist in the identification of the mutation and in research toward novel treatments that target aberrant metabolism in IDH1-mutant
glioma.