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Distinct metabolic ...
Distinct metabolic hallmarks of WHO classified adult glioma subtypes
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- Björkblom, Benny (author)
- Umeå universitet,Kemiska institutionen
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- Wibom, Carl (author)
- Umeå universitet,Onkologi
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- Eriksson, Maria (author)
- Umeå universitet,Onkologi
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- Bergenheim, A. Tommy (author)
- Umeå universitet,Neurovetenskaper
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- Sjöberg, Rickard L. (author)
- Umeå universitet,Neurovetenskaper
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- Jonsson, Pär (author)
- Umeå universitet,Kemiska institutionen
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- Brännström, Thomas (author)
- Umeå universitet,Patologi
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- Antti, Henrik, 1970- (author)
- Umeå universitet,Kemiska institutionen
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- Sandström, Maria (author)
- Umeå universitet,Onkologi
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- Melin, Beatrice S. (author)
- Umeå universitet,Onkologi
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(creator_code:org_t)
- 2022-02-14
- 2022
- English.
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In: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 24:9, s. 1454-1468
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Astrocytoma
- Glioblastoma
- Metabolic reprogramming
- Oligodendroglioma
- WHO classification
- molekylärbiologi
- Molecular Biology
- Pathology
- patologi
- Oncology
- onkologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Björkblom, Benny
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Wibom, Carl
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Eriksson, Maria
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Bergenheim, A. T ...
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Sjöberg, Rickard ...
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Jonsson, Pär
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show more...
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Brännström, Thom ...
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Antti, Henrik, 1 ...
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Sandström, Maria
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Melin, Beatrice ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Neuro-Oncology
- By the university
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Umeå University