title: Proteomic analysis of oligodendrogliomas expressing a mutant isocitrate dehydrogenase-1.
abstract: Gliomas are primary tumors of the human central nervous system with unknown mechanisms of progression. Isocitrate dehydrogenase-1 (IDH1) mutation is frequent in diffuse gliomas such as oligodendrogliomas. To gain insights into the physiopathology of oligodendrogliomas that have a better prognosis than other diffuse gliomas, we combined microdissection, 2-D DIGE and MS/MS focusing on proteome alterations associated with IDH1 mutation. We first compared tumor tissues (TT) and minimally infiltrated parenchymal tissues (MIT) of four IDH1-mutated oligodendrogliomas to verify whether proteins specific to oligodendroglioma tumor cells could be identified from one patient to another. This study resulted in identification of 68 differentially expressed proteins, with functions related to growth of tumor cells in a nervous parenchyma. We then looked for proteins distinctly expressed in TT harboring either mutant (oligodendrogliomas, n=4) or wild-type IDH1 (oligodendroglial component of malignant glio-neuronal tumors, n=4). This second analysis resulted in identification of distinct proteome patterns composed of 42 proteins. Oligodendrogliomas with a mutant IDH1 had noteworthy enhanced expression of enzymes controlling aerobic glycolysis and detoxification, and anti-apoptosis proteins. In addition, the mutant IDH1 migrated differently from the wild-type IDH1 form. Comparative proteomic analysis might thus be suitable to identify proteome alterations associated with a well-defined mutation.
authors: Inserm U894, Centre de Psychiatrie et Neurosciences, Lab. Plasticité Gliale, Paris, France.
authors: Cécile
authors: C
authors: Thirant
authors: Pascale
authors: P
authors: Varlet
authors: Joanna
authors: J
authors: Lipecka
authors: Morgane
authors: M
authors: Le Gall
authors: Cédric
authors: C
authors: Broussard
authors: Philippe
authors: P
authors: Chafey
authors: Jeanne-Marie
authors: JM
authors: Studler
authors: Joelle
authors: J
authors: Lacombe
authors: Séverin
authors: S
authors: Lions
authors: Angélique
authors: A
authors: Guillaudeau
authors: Luc
authors: L
authors: Camoin
authors: Catherine
authors: C
authors: Daumas-Duport
authors: Marie-Pierre
authors: MP
authors: Junier
authors: Hervé
authors: H
authors: Chneiweiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D009154:Mutation; D009837:Oligodendroglioma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods
chemical_list: D020543:Proteome; D007521:Isocitrate Dehydrogenase