Open AccessDetection of 2‐Hydroxyglutarate in Formalin‐Fixed Paraffin‐Embedded Glioma Specimens by Gas Chromatography/Mass Spectrometry
Author(s) -
Sahm Felix,
Capper David,
Pusch Stefan,
Balss Jörg,
Koch Arend,
Langhans ClausDieter,
Okun Jürgen G.,
von Deimling Andreas
Publication year - 2012
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2011.00506.x
Subject(s) - isocitrate dehydrogenase , mass spectrometry , oligodendroglioma , chemistry , idh1 , glioma , astrocytoma , microbiology and biotechnology , chromatography , cancer research , biology , mutant , biochemistry , gene , enzyme
Mutations in the isocitrate dehydrogenase ( IDH ) 1 and 2 genes occur frequently in diffuse astrocytoma and oligodendroglioma. The consecutive amino acid substitutions in the mutant proteins result in a gain of the function to catalyze the reduction of alpha‐ketoglutarate to 2‐hydroxyglutarate (2HG). So far, all investigated IDH mutations share this gain of function. We here describe a method to detect 2HG levels in archival formalin‐fixed paraffin‐embedded tumor specimens by stable isotope dilution using gas chromatography followed by mass spectrometry (GC/MS). While 2HG levels are notably decreased during the routine embedding process, preserved amounts are still sufficient to indicate a mutation. Detection of 2HG in archival specimens could make routinely processed tissue accessible for research on 2HG accumulation and may allow studies on correlation with clinical data.