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Distinct metabolic hallmarks of WHO classified adult glioma subtypes
Umeå University, Faculty of Science and Technology, Department of Chemistry.ORCID iD: 0000-0001-9347-5790
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
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2022 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 24, no 9, p. 1454-1468, article id noac042Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Gliomas are complex tumors with several genetic aberrations and diverse metabolic programs contributing to their aggressive phenotypes and poor prognoses. This study defines key metabolic features that can be used to differentiate between glioma subtypes, with potential for improved diagnostics and subtype targeted therapy.

METHODS: Cross-platform global metabolomic profiling coupled with clinical, genetic, and pathological analysis of glioma tissue from 224 tumors - oligodendroglioma (n=31), astrocytoma (n=31) and glioblastoma (n=162) - were performed. Identified metabolic phenotypes were evaluated in accordance with the WHO classification, IDH-mutation, 1p/19q-codeletion, WHO-grading 2-4, and MGMT promoter methylation.

RESULTS: Distinct metabolic phenotypes separate all six analyzed glioma subtypes. IDH-mutated subtypes, expressing 2-hydroxyglutaric acid, were clearly distinguished from IDH-wildtype subtypes. Considerable metabolic heterogeneity outside of the mutated IDH pathway were also evident, with key metabolites being high expression of glycerophosphates, inositols, monosaccharides and sugar alcohols and low levels of sphingosine and lysoglycerophospholipids in IDH-mutants. Among the IDH-mutated subtypes, we observed high levels of amino acids, especially glycine and 2-aminoadipic acid, in grade 4 glioma, and N-acetyl aspartic acid in low-grade astrocytoma and oligodendroglioma. Both IDH-wildtype and mutated oligodendroglioma and glioblastoma were characterized by high levels of acylcarnitines, likely driven by rapid cell growth and hypoxic features. We found elevated levels of 5-HIAA in gliosarcoma and a subtype of oligodendroglioma not yet defined as a specific entity, indicating a previously not described role for the serotonin pathway linked to glioma with bimorphic tissue.

CONCLUSION: Key metabolic differences exist across adult glioma subtypes.

Place, publisher, year, edition, pages
Oxford University Press, 2022. Vol. 24, no 9, p. 1454-1468, article id noac042
Keywords [en]
Astrocytoma, Glioblastoma, Metabolic reprogramming, Oligodendroglioma, WHO classification
National Category
Cancer and Oncology
Research subject
Molecular Biology; Pathology; Oncology
Identifiers
URN: urn:nbn:se:umu:diva-192529DOI: 10.1093/neuonc/noac042ISI: 000785708300001PubMedID: 35157758Scopus ID: 2-s2.0-85137137374OAI: oai:DiVA.org:umu-192529DiVA, id: diva2:1658661
Funder
Swedish Cancer Society, 2018/390Swedish Cancer Society, 2013/0291Swedish Cancer Society, 19 0370Swedish Research Council, 2019-01566Cancerforskningsfonden i Norrland, AMP17-899Cancerforskningsfonden i Norrland, AMP17- 882Sjöberg Foundation, 2020-01-07-08Available from: 2022-05-17 Created: 2022-05-17 Last updated: 2023-05-23Bibliographically approved

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Björkblom, BennyWibom, CarlEriksson, MariaBergenheim, A. TommySjöberg, Rickard L.Jonsson, PärBrännström, ThomasAntti, HenrikSandström, MariaMelin, Beatrice S.

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Björkblom, BennyWibom, CarlEriksson, MariaBergenheim, A. TommySjöberg, Rickard L.Jonsson, PärBrännström, ThomasAntti, HenrikSandström, MariaMelin, Beatrice S.
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