Caroline Bund1,2, Mariana Guergova-Kuras3, A Ercument Cicek4,5, François-Marie Moussallieh6, Nassim Dali-Youcef7,8, Martial Piotto9, Pilar Schneider3, Rémy Heller10, Natacha Entz-Werle11, Benoît Lhermitte12, Marie-Pierre Chenard12, Roland Schott13, François Proust14, Georges Noël15, Izzie Jacques Namer6,16,17. 1. Service de Biophysique et Médecine Nucléaire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 1, Avenue Molière, 67098, Strasbourg Cedex 09, France. Caroline.BUND@chru-strasbourg.fr. 2. ICube, Université de Strasbourg/CNRS, UMR 7357, Strasbourg, France. Caroline.BUND@chru-strasbourg.fr. 3. Ariana Pharmaceuticals SA, Paris, France. 4. Lane Center of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, USA. 5. Computer Engineering Department, Bilkent University, Ankara, Turkey. 6. Service de Biophysique et Médecine Nucléaire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 1, Avenue Molière, 67098, Strasbourg Cedex 09, France. 7. IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire)/CNRS UMR 7104/INSERM U964, Université de Strasbourg, Strasbourg, France. 8. Laboratoire de Biochimie et Biologie Moléculaire, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 9. Bruker Biospin, Wissembourg, France. 10. Laboratoire de Microbiologie et Biologie Moléculaire, Hôpitaux Civils de Colmar, Colmar, France. 11. Service de Pédiatrie Onco-hématologie, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 12. Service d'Anatomie Pathologique, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 13. Departement d'Oncologie Médicale, Centre Paul Strauss, Strasbourg, France. 14. Service de Neurochirurgie, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 15. Departement de Radiothérapie, Centre Paul Strauss, Strasbourg, France. 16. ICube, Université de Strasbourg/CNRS, UMR 7357, Strasbourg, France. 17. FMTS (Fédération de Médecine Translationnelle de Strasbourg), Faculté de Médecine, Strasbourg, France.
Abstract
INTRODUCTION: The identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential. OBJECTIVES: The aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O6-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time. METHODS: We applied 1H high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to 72 resected oligodendrogliomas. RESULTS: The presence of IDH1, TP53, 1p19q codeletion, MGMT promoter methylation reduced the relative risk of death, whereas PTEN methylation and EGFR amplification were associated with poor prognosis. Increased concentration of 2-hydroxyglutarate (2HG), N-acetyl-aspartate (NAA), myo-inositol and the glycerophosphocholine/phosphocholine (GPC/PC) ratio were good prognostic factors. Increasing the concentration of serine, glycine, glutamate and alanine led to an increased relative risk of death. CONCLUSION: HRMAS NMR spectroscopy provides accurate information on the metabolomics of oligodendrogliomas, making it possible to find new biomarkers indicative of survival. It enables rapid characterization of intact tissue and could be used as an intraoperative method.
INTRODUCTION: The identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential. OBJECTIVES: The aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O6-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time. METHODS: We applied 1H high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy to 72 resected oligodendrogliomas. RESULTS: The presence of IDH1, TP53, 1p19q codeletion, MGMT promoter methylation reduced the relative risk of death, whereas PTEN methylation and EGFR amplification were associated with poor prognosis. Increased concentration of 2-hydroxyglutarate (2HG), N-acetyl-aspartate (NAA), myo-inositol and the glycerophosphocholine/phosphocholine (GPC/PC) ratio were good prognostic factors. Increasing the concentration of serine, glycine, glutamate and alanine led to an increased relative risk of death. CONCLUSION: HRMAS NMR spectroscopy provides accurate information on the metabolomics of oligodendrogliomas, making it possible to find new biomarkers indicative of survival. It enables rapid characterization of intact tissue and could be used as an intraoperative method.
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