title: Diagnostic value of plasma and urinary 2-hydroxyglutarate to identify patients with isocitrate dehydrogenase-mutated glioma.
abstract: BACKGROUND
  Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma.
  
  
  METHODS
  All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry.
  
  
  RESULTS
  A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment.
  
  
  CONCLUSIONS
  Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients.
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy giuseppe.lombardi@ioveneto.it.
authors: Giuseppe
authors: G
authors: Lombardi
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Giuseppe
authors: G
authors: Corona
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Luisa
authors: L
authors: Bellu
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Alessandro
authors: A
authors: Della Puppa
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Ardi
authors: A
authors: Pambuku
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Pasquale
authors: P
authors: Fiduccia
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Roberta
authors: R
authors: Bertorelle
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Marina Paola
authors: MP
authors: Gardiman
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Domenico
authors: D
authors: D'Avella
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Giuseppe
authors: G
authors: Toffoli
authors: Department of Clinical and Experimental Oncology, Medical Oncology 1, Clinical Trials and Biostatistics Unit, and Molecular Immunology and Oncology Unit, Veneto Institute of Oncology-IRCCS, Padua, Italy; Experimental and Clinical Pharmacology, National Cancer Institute, Aviano, Italy; Neurosurgery Department and Pathology Department, Neurological Sciences, Padua Hospital, Padua, Italy; Neurosurgery Department, University of Padua, Padua, Italy.
authors: Vittorina
authors: V
authors: Zagonel
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D005260:Female; D005910:Glioma / Q000097:blood / Q000235:genetics / Q000652:urine; D005977:Glutarates / Q000097:blood / Q000652:urine; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor; D005977:Glutarates; C019417:alpha-hydroxyglutarate; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: 2-Hydroxyglutarate; Biomarker; Glioma; Isocitrate dehydrogenase; Plasma; Urine