Gliomas are heterogeneous tumours derived from glial cells and remain the deadliest form of brain cancer. Although the glioma stem cell sits at the apex of the cellular hierarchy, how it produces the vast cellular constituency associated with frank glioma remains poorly defined. We explore glioma tumorigenesis through the lens of glial development, starting with the neurogenic–gliogenic switch and progressing through oligodendrocyte and astrocyte differentiation. Beginning with the factors that influence normal glial linage progression and diversity, a pattern emerges that has useful parallels in the development of glioma and may ultimately provide targetable pathways for much-needed new therapeutics.
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The authors thank C. Gillespie for editing and reviewing this manuscript. This work was supported by grants from the US National Institutes of Health (NS071153 to B.D. and K01CA190235 and 5-T32HL092332-08 to S.M.G.) and the Cancer Prevention Research Institute of Texas (RP150334 and RP160192 to B.D.).
Nature Reviews Neuroscience thanks B. Appel, W. Weiss, M. Monje and the other, anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interest.
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- Isocitrate dehydrogenase (IDH) status
Refers to whether a patient possesses a missense mutation in IDH1 or IDH2 that has been linked to glioma.
- Frank glioma
A clinically diagnosed glioma.
A commonly used animal tumour model in which patient-derived cancer cells are transplanted under the skin or into the organ of interest in immune-deficient animals.
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Laug, D., Glasgow, S.M. & Deneen, B. A glial blueprint for gliomagenesis. Nat Rev Neurosci 19, 393–403 (2018). https://doi.org/10.1038/s41583-018-0014-3
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