Mass spectrometry of gangliosides in extracranial tumors: Application to adrenal neuroblastoma.
We report here on the introduction of mass spectrometry (MS) for profiling of native gangliosides from an extracranial tumor. The analytical approach was based on a modern platform combining the superior sensitivity and reproducibility of fully automated chip-based nanoelectrospray ionization (nanoESI) with the high resolution and mass accuracy provided by a hybrid quadrupole time-of-flight (QTOF) instrument. The feasibility of the method for the analysis of gangliosides, which are much less expressed in extracranial tissues, was here tested using as the model substrate an adrenal neuroblastoma (NB) specimen located in the abdominal region of a 2-year-old infant. Under properly optimized conditions, MS profiling revealed information on at least 61 different gangliosides exhibiting heterogeneity of the glycan and lipid compositions. NB was found dominated by species bearing short-chain oligosaccharide cores with a reduced overall Neu5Ac content. By chip-nanoESI MS, preceding findings related to the GD2 role in NB were confirmed. Moreover, the screening experiments offered novel information supporting the possible biomarker role of GM4, GM3, and GM1 ganglioside classes. Structural analysis of GM1(d18:1/18:2) and GD1(d18:0/19:0) possibly tumor-associated markers, carried out by tandem MS (MS/MS) using collision-induced dissociation (CID) at low energies, indicated that both GM1a and GD1b isomers are present in NB.
Mass Spectrometry Laboratory, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300224 Timisoara, Romania; Faculty of Physics, West University of Timisoara, 300223 Timisoara, Romania.
Adrian C
AC
Robu
Department of Chemistry and Biochemistry, Faculty of Medicine, University of Zagreb, 10000, Šalata, Zagreb, Croatia.
Željka
Ž
Vukelić
Department of Paediatrics, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania.
Catalin
C
Schiopu
Department of Paediatrics, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania.
Florina
F
Capitan
Mass Spectrometry Laboratory, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300224 Timisoara, Romania; Laboratory for the Analysis and Modeling of Biological Systems, "Aurel Vlaicu" University of Arad, 310130 Arad, Romania. Electronic address: alina.zamfir@uav.ro.
Alina D
AD
Zamfir
D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D005732:Gangliosides / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D009447:Neuroblastoma / Q000378:metabolism*
D005732:Gangliosides
Chip–nanoelectrospray; Extracranial tumors; Fragmentation analysis; Gangliosides; High-resolution mass spectrometry; Neuroblastoma