An integrated genomic and metabolomic approach for defining survival time in adult oligodendrogliomas patients

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.