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BI-27 * ANALYSIS OF THE BIOCHEMICAL PROFILE OF LOW GRADE GLIOMA WITH DIFFERENT IDH1 MUTATION STATUS USING VIBRATIONAL SPECTROSCOPY

2014; Oxford University Press; Volume: 16; Issue: suppl 5 Linguagem: Inglês

10.1093/neuonc/nou239.27

1523-5866

Ortrud Uckermann, Tareq A. Juratli, Marina Clemente Conde, Roberta Galli, Dietmar Krex, Kathrin Geiger, Gabriele Schackert, Achim Temme, Gerald Steiner, Matthias Kirsch,

Metabolomics and Mass Spectrometry Studies

Mutations in human cytosolic isocitrate dehydrogenases 1 (IDH1) are a common feature of low grade gliomas (LGG) and cause profound changes of the metabolites of the Krebs cycle. Vibrational spectroscopy comprises label-free techniques that probe a sample's molecular composition. Therefore, we investigated the ability of fourier-transform infrared (FT-IR) spectroscopy to analyze the IDH1-mutation status in cell culture systems and human brain tumor samples. Cell lines (U87-MG, SVG p12 and the primary glioblastoma cell lines HT7606, HT12346 and HT12347) were transduced with either IDH1 wild-type or mutated IDH1. Clusteranalysis and principal-component-analysis were able to detect differences in the respective FT-IR spectral datasets in regions assigned to saccharides (1050 and 1120 cm−1) and proteins (1236, 1545 and 1651 cm−1). Brain tumor samples of human LGG were obtained during routine surgery and the IDH1 mutation status was determined by DNA sequencing (n = 17). Difference spectra (IDH1-mut vs. IDH1-wt) showed changes in the region around 1100 cm−1 which is attributed to saccharides. Additionally, amide I and amide II spectral bands (around 1550 and 1650 cm−1, respectively) were reduced in the IDH1-mut dataset whereas the band at 1740 cm−1 assigned to C = O stretching vibrations was more pronounced. Principal-component-analysis confirmed differences between the two groups based on spectral regions assigned to saccharides, proteins and to C = O stretching vibrations, as identified previously in the difference spectra. Supervised classification recognized relevant spectral regions at 974, 1005, 1038-1044, 1078-1082, 1267-1275, 1342, 1417-1421, 1479 cm−1 and was able to assign 16 of the 17 tumor samples to the correct group. On the basis of FT-IR spectroscopy samples of LGG carrying IDH1 mutations can be discerned from IDH1 wildtype tumors. Relevant spectral regions assigned to saccharides and C = O stretching vibrations can be explained by changes in the Krebs cycle and in particular by the accumulation of 2-hydroxyglutarate (rich in C = O bonds).