Abstract #0427
Metabolomic assessment of succinate dehydrogenase dysfunction in pheochromocytomas and paragangliomas by 1H-HRMAS NMR spectroscopy: clinical and pathophysiological implications
Alessio Imperiale 1,2 , Stphanie Battini 1 , Philippe Roche 3 , Franois-Marie Moussallieh 1 , Ercument A Cicek 4 , Frdric Sebag 5 , Laurent Brunaud 6 , Anne Barlier 7 , Karim Elbayed 1 , Anderson Loundou 8 , Philippe Bachellier 9 , Bernard Goichot 10 , Constantine A Stratakis 11,12 , Karel Pacak 13,14 , David Taieb 15 , and Izzie-Jacques Namer 1,2
1
ICube laboratory UMR 7357, University of
Strasbourg/CNRS and FMTS, Strasbourg, France,
2
University
Hospitals of Strasbourg, Department of Biophysics and
Nuclear Medicine, Hautepierre Hospital, Strasbourg,
France,
3
Integrative
Structural & Chemical Biology (iSCB) & INT-3D Molecular
Modeling Platform, Cancer Resear, CNRS UMR7258; INSERM
U1068; Institut Paoli Calmettes; Aix-Marseille
University UM105, Marseille, France,
4
Lane
Center for Computational Biology, School of Computer
Science, Carnegie Mellon University, 5000 Forbes Ave,
Pittsburgh, PA 15222, United States,
5
Department
of Endocrine Surgery, La Timone University Hospital,
Aix-Marseille University, Marseille, France,
6
Department
of Digestive, Hepato-Biliary and Endocrine Surgery,
Brabois University Hospital, Nancy, France,
7
Laboratory
of Biochemistry and Molecular Biology, Conception
Hospital, Aix-Marseille, University, Marseille, France,
8
Department
of Public Health, Aix-Marseille University, Marseille,
France,
9
Department
of Visceral Surgery and Transplantation, Hautepierre
Hospital, University Hospitals of Strasbourg,
Strasbourg, France,
10
Department
of Internal Medicine, Diabetes and Metabolic Disorders,
Hautepierre Hospital, University Hospitals of
Strasbourg, Strasbourg, France,
11
Section
on Genetics and Endocrinology (SEGEN), Program on
Developmental Endocrinology and Genetics (PDEGEN),
Bethesda, United States,
12
Eunice
Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health,
Bethesda, United States,
13
Program in
Reproductive and Adult Endocrinology, Eunice Kennedy
Shriver National Institute of Child Health and Human
Development, Bethesda, United States,
14
National
Institutes of Health, Bethesda, United States,
15
La
Timone University Hospital, European Center for Research
in Medical Imaging, Marseille, France
Pheochromocytomas/paragangliomas (PHEOs/PGLs) are
characterized by high genetic heterogeneity. Mutations
in succinate dehydrogenase genes (SDHx) increase
susceptibility to develop PHEOs/PGLs. The SDHx genes
encode the SDH enzyme that catalyzes the oxidation of
succinate to fumarate in the tricarboxylic acid cycle
(TCA) and the respiratory chain. The aim of the present
study was to investigate the HRMAS NMR-based metabolomic
profiling of PHEOs/PGLs in order to: (a) define the
global metabolomic profile of the SDH-related PHEOs/PGLs
in comparison to sporadic tumors and (b) identify
metabolites that could be used as clinical predictors of
SDH deficiency
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