Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry
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Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry. / Longuespée, Rémi; Wefers, Annika K; De Vita, Elena; Miller, Aubry K; Reuss, David E; Wick, Wolfgang; Herold-Mende, Christel; Kriegsmann, Mark; Schirmacher, Peter; von Deimling, Andreas; Pusch, Stefan.
In: ACTA NEUROPATHOL COM, Vol. 6, No. 1, 02.03.2018, p. 21.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry
AU - Longuespée, Rémi
AU - Wefers, Annika K
AU - De Vita, Elena
AU - Miller, Aubry K
AU - Reuss, David E
AU - Wick, Wolfgang
AU - Herold-Mende, Christel
AU - Kriegsmann, Mark
AU - Schirmacher, Peter
AU - von Deimling, Andreas
AU - Pusch, Stefan
PY - 2018/3/2
Y1 - 2018/3/2
N2 - All isocitrate dehydrogenase (IDH) mutant solid neoplasms exhibit highly elevated levels of D-2-hydroxyglutarate (D-2HG). Detection of 2HG in tumor tissues currently is performed by gas or liquid chromatography-mass spectrometry (GC- or LC-MS) or biochemical detection. While these methods are highly accurate, a considerable amount of time for tissue preparation and a relatively high amount of tissue is required for testing. We here present a rapid approach to detect 2HG in brain tumor tissue based on matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF). We analyzed 26 brain tumor samples with known IDH1 or IDH2 mutation and compared readouts to those from 28 brain tumor samples of wildtype IDH status. IDH mutant samples exhibited a clear positive signal for 2HG which was not observed in any of the IDH wildtype tumors. Our analytical pipeline allowed for 2HG detection in less than 5 min. Data were validated by determining 2HG levels in all tissues with a biochemical assay. In conclusion, we developed a protocol for rapid detection of 2HG levels and illustrate the possibility to use MALDI-TOF for the detection of metabolites on frozen tissue sections in a diagnostic setting.
AB - All isocitrate dehydrogenase (IDH) mutant solid neoplasms exhibit highly elevated levels of D-2-hydroxyglutarate (D-2HG). Detection of 2HG in tumor tissues currently is performed by gas or liquid chromatography-mass spectrometry (GC- or LC-MS) or biochemical detection. While these methods are highly accurate, a considerable amount of time for tissue preparation and a relatively high amount of tissue is required for testing. We here present a rapid approach to detect 2HG in brain tumor tissue based on matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF). We analyzed 26 brain tumor samples with known IDH1 or IDH2 mutation and compared readouts to those from 28 brain tumor samples of wildtype IDH status. IDH mutant samples exhibited a clear positive signal for 2HG which was not observed in any of the IDH wildtype tumors. Our analytical pipeline allowed for 2HG detection in less than 5 min. Data were validated by determining 2HG levels in all tissues with a biochemical assay. In conclusion, we developed a protocol for rapid detection of 2HG levels and illustrate the possibility to use MALDI-TOF for the detection of metabolites on frozen tissue sections in a diagnostic setting.
KW - Biomarkers, Tumor/analysis
KW - Brain/metabolism
KW - Brain Chemistry
KW - Brain Neoplasms/chemistry
KW - Cryopreservation
KW - Glioma/chemistry
KW - Glutarates/analysis
KW - Humans
KW - Immunohistochemistry
KW - Isocitrate Dehydrogenase/genetics
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
KW - Time Factors
U2 - 10.1186/s40478-018-0523-3
DO - 10.1186/s40478-018-0523-3
M3 - SCORING: Journal article
C2 - 29499756
VL - 6
SP - 21
JO - ACTA NEUROPATHOL COM
JF - ACTA NEUROPATHOL COM
SN - 2051-5960
IS - 1
ER -
