Executive Summary : | "The World Health Organization (WHO) has classified gliomas into various molecular subtypes based on genetic and epigenetic events, such as mutations in isocitrate dehydrogenase (IDH), 1p19q (codeleted or intact), epigenetically methylated MGMT, or unmethylated-MGMT. Oligodendrogliomas, slow-growing gliomas, harbor IDH mutations with 1p19q codeletion, while astrocytoma, the fast-growing gliomas, lack 1p19q codeletion. A subset of rapidly growing malignant Grade-4 gliomas (GBM) have epigenetically methylated MGMT gene (presents with good prognosis) and unmethylated MGMT (presents with bad prognosis).
The study aims to examine whether intracellular metabolic pools, substrates, and pathways driving proliferation of IDH mutant gliomas are distinct than IDH wild type gliomas. It also aims to perform comprehensive Proton-NMR spectroscopy investigations of media samples taken before and after 5 days of cell culture of glioma cell lines to investigate the Consumption and Release (CORE) of metabolites such as glucose, acetate, glutamine, glycine, serine, choline, lactate, glutathione, and β-hydroxy butyrate (relevant for cell proliferation). The NMR investigations will reveal whether the consumption and release of metabolites are unique for slow-growing, fast-growing, and rapidly growing gliomas characterized by molecular subtypes. The study aims to unravel the metabolic targets associated with slow-growing, good prognosis (1p19q codeleted and IDH mutant) vs. fast-growing, bad prognosis (1p19q intact) gliomas and elucidate the metabolic phenotype of MGMT-methylated glioblastomas vs. MGMT-unmethylated gliomas." |