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- W4210660331 abstract "The transcriptomic classification of glioblastoma (GBM) has failed to predict survival and therapeutic vulnerabilities. A computational approach for unbiased identification of core biological traits of single cells and bulk tumors uncovered four tumor cell states and GBM subtypes distributed along neurodevelopmental and metabolic axes, classified as proliferative/progenitor, neuronal, mitochondrial and glycolytic/plurimetabolic. Each subtype was enriched with biologically coherent multiomic features. Mitochondrial GBM was associated with the most favorable clinical outcome. It relied exclusively on oxidative phosphorylation for energy production, whereas the glycolytic/plurimetabolic subtype was sustained by aerobic glycolysis and amino acid and lipid metabolism. Deletion of the glucose-proton symporter SLC45A1 was the truncal alteration most significantly associated with mitochondrial GBM, and the reintroduction of SLC45A1 in mitochondrial glioma cells induced acidification and loss of fitness. Mitochondrial, but not glycolytic/plurimetabolic, GBM exhibited marked vulnerability to inhibitors of oxidative phosphorylation. The pathway-based classification of GBM informs survival and enables precision targeting of cancer metabolism. PMID: 33681822 Funding information This work was supported by: NCI NIH HHS, United States Grant ID: R01 CA239721 NCI NIH HHS, United States Grant ID: R01 CA178546 NCI NIH HHS, United States Grant ID: R01 CA131126 NCI NIH HHS, United States Grant ID: R01 CA179044 NCI NIH HHS, United States Grant ID: U54 CA193313 NCI NIH HHS, United States Grant ID: R01 CA101644 NCI NIH HHS, United States Grant ID: R01 CA190891 NINDS NIH HHS, United States Grant ID: R01 NS103473 NCI NIH HHS, United States Grant ID: R01 CA239698 More Less keyboard_arrow_down" @default.
- W4210660331 created "2022-02-08" @default.
- W4210660331 creator A5019503467 @default.
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- W4210660331 date "2021-05-17" @default.
- W4210660331 modified "2023-09-27" @default.
- W4210660331 title "Faculty Opinions recommendation of Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities." @default.
- W4210660331 doi "https://doi.org/10.3410/f.739341152.793585340" @default.
- W4210660331 hasPublicationYear "2021" @default.
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