Patients with
malignant gliomas have a poor prognosis with average survival of less than 1 year. Whereas in other
tumor entities the characteristics of
tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in
brain tumors, notably in
gliomas. One metabolic feature characteristic of
gliomas, in particular diffuse
astrocytomas and oligodendroglial
tumors, is the variable content of
D-2-hydroxyglutarate (D2HG), a metabolite that was discovered first in this
tumor entity. D2HG is generated in large amounts due to various "gain-of-function" mutations in the
isocitrate dehydrogenases IDH1 and IDH2. Meanwhile, D2HG has been detected in several other
tumor entities, including intrahepatic bile-duct
cancer,
chondrosarcoma,
acute myeloid leukemia, and angioimmunoblastic
T-cell lymphoma. D2HG is barely detectable in healthy tissue (<0.1 mM), but its concentration increases up to 35 mM in malignant
tumor tissues. Consequently, the "oncometabolite" D2HG has gained increasing interest in the field of
tumor metabolism. To facilitate its quantitative measurement without loss of spatial resolution at a microscopical level, we have developed a novel bioluminescence assay for determining D2HG in sections of snap-frozen tissue. The assay was verified independently by photometric tests and liquid chromatography/mass spectrometry. The novel technique allows the microscopically resolved determination of D2HG in a concentration range of 0-10 μmol/g tissue (wet weight). In combination with the already established bioluminescence imaging techniques for
ATP,
glucose,
pyruvate, and
lactate, the novel D2HG assay enables a comparative characterization of the metabolic profile of individual
tumors in a further dimension.