gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

Accumulation of 2-hydroxyglutarate is not a biomarker for malignant progression in IDH-mutated low-grade gliomas

Meeting Abstract

  • Tareq A. Juratli - Klinik und Polklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • Mirko Peitzsch - Abteilung für klinische Chemie und Labormedizin, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • Kathrin Geiger - Neuropathologie, Institut für Pathologie, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • Gabriele Schackert - Klinik und Polklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • Graeme Eisenhofer - Abteilung für klinische Chemie und Labormedizin, Universitätsklinikum Carl Gustav Carus der TU Dresden
  • Dietmar Krex - Klinik und Polklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus der TU Dresden

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocMI.07.05

doi: 10.3205/13dgnc335, urn:nbn:de:0183-13dgnc3350

Published: May 21, 2013

© 2013 Juratli et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: To determine whether the accumulation of 2-hydroxyglutarate in IDH-mutated low-grade gliomas WHO grade II (LGG) correlates with their malignant transformation and to evaluate changes in metabolite levels during malignant progression.

Method: Samples from 54 patients were screened for IDH mutations: 18 patients with both LGG and their consecutive secondary glioblastomas (sGBM) (n=36), 19 patients with LGG without malignant transformation, 10 patients with primary glioblastomas (pGBM), and 7 non-glioma patients. The cellular tricarboxylic acid cycle metabolites – citrate, isocitrate, 2-hydroxyglutarate, α-ketoglutarate, fumarate, and succinate – were profiled by liquid chromatography – tandem mass spectrometry. Ratios of 2-hydroxyglutarate/isocitrate were used to evaluate differences in 2-hydroxyglutarate accumulation in tumors from LGG- and sGBM-groups compared to pGBM and non-glioma groups.

Results: IDH1 mutations were detected in 27 out of 37 LGG patients (77.1%). In addition, in LGG patients with malignant progression (n=18), 16 patients were IDH1 mutated with a stable mutation status during their malignant progression. None of the pGBM or non-glioma tumor patients had an IDH mutation. Increased 2-hydroxyglutarate/isocitrate ratios were seen in patients with IDH1 mutated LGG and sGBM in comparison to those with IDH1 non-mutated LGG, pGBM, and non-glioma groups. However, no differences in intratumoral 2-hydroxyglutarate/isocitrate ratios were found between LGG patients with and without malignant transformation. Furthermore, in patients with paired samples of LGG and their consecutive sGBM, the 2-hydroxyglutarate/isocitrate ratios did not differ between the two tumor stages.

Conclusions: Although intratumoral 2-hydroxyglutarate accumulation provides a marker for the presence of IDH mutations, the metabolite is not a useful biomarker for identifying malignant transformation or evaluating malignant progression.