title: A new specific succinate-glutamate metabolomic hallmark in SDHx-related paragangliomas.
abstract: Paragangliomas (PGLs) are frequently associated with germline mutations in genes involved in energy metabolism. The purpose of the present study was to assess whether the tumor metabolomic profile of patients with hereditary and apparently sporadic PGLs enables the distinction of different subtypes of tumors. Twenty-eight unrelated patients with a histological diagnosis of PGLs were included in the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD), 6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients (one per patient) were evaluated with (1)H high-resolution magic angle spinning (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007 vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were found to have the highest values of glutathione (GSH) compared to other tumors. Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were accurately distinguished from the other ones on both 3- and 2-class PLS-DA models. The present study shows that HRMAS NMR spectroscopy is a very promising method for investigating the metabolomic profile of various PGLs. The present data suggest the existence of a specific succinate-glutamate hallmark of SDHx PGLs. The relevance of such a metabolomic hallmark is expected to be very useful in designing novel treatment options as well as improving the diagnosis and follow-up of these tumors, including metastatic ones.
authors: Department of Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, Strasbourg, France ; ICube, UMR (Unité Mixte de Recherche) 7357 University of Strasbourg/CNRS (Centre National de la Recherche Scientifique) and FMTS (Fédération de médecine translationnelle de Strasbourg), Faculty of Medicine, Strasbourg, France.
authors: Alessio
authors: A
authors: Imperiale
authors: François-Marie
authors: FM
authors: Moussallieh
authors: Frédéric
authors: F
authors: Sebag
authors: Laurent
authors: L
authors: Brunaud
authors: Anne
authors: A
authors: Barlier
authors: Karim
authors: K
authors: Elbayed
authors: Philippe
authors: P
authors: Bachellier
authors: Bernard
authors: B
authors: Goichot
authors: Karel
authors: K
authors: Pacak
authors: Izzie-Jacques
authors: IJ
authors: Namer
authors: David
authors: D
authors: Taïeb
mesh_terms: D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D055432:Metabolomics / Q000379:methods; D008954:Models, Biological; D010235:Paraganglioma / Q000235:genetics / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D019802:Succinic Acid; D013385:Succinate Dehydrogenase