Glioma

Abstract

Gliomas are primary brain tumours that are thought to derive from neuroglial stem or progenitor cells. On the basis of their histological appearance, they have been traditionally classified as astrocytic, oligodendroglial or ependymal tumours and assigned WHO grades I–IV, which indicate different degrees of malignancy. Tremendous progress in genomic, transcriptomic and epigenetic profiling has resulted in new concepts of classifying and treating gliomas. Diffusely infiltrating gliomas in adults are now separated into three overarching tumour groups with distinct natural histories, responses to treatment and outcomes: isocitrate dehydrogenase (IDH)-mutant, 1p/19q co-deleted tumours with mostly oligodendroglial morphology that are associated with the best prognosis; IDH-mutant, 1p/19q non-co-deleted tumours with mostly astrocytic histology that are associated with intermediate outcome; and IDH wild-type, mostly higher WHO grade (III or IV) tumours that are associated with poor prognosis. Gliomas in children are molecularly distinct from those in adults, the majority being WHO grade I pilocytic astrocytomas characterized by circumscribed growth, favourable prognosis and frequent BRAF gene fusions or mutations. Ependymal tumours can be molecularly subdivided into distinct epigenetic subgroups according to location and prognosis. Although surgery, radiotherapy and alkylating agent chemotherapy are still the mainstay of treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles may ultimately improve outcome. For an illustrated summary of this Primer, visit: http://go.nature.com/TXY7Ri

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Figure 1: Relative frequency of primary brain and central nervous system tumours.
Figure 2: Brain cells and brain tumours.
Figure 3: Age-adjusted incidence of primary brain and central nervous system tumours by histology and age group.
Figure 4: Important genetic and epigenetic alterations in the different types of gliomas.
Figure 5: Biochemical consequences of glioma-associated isocitrate dehydrogenase mutations.
Figure 6: Neuroimaging and histological features of gliomas.
Figure 7: Molecular marker-based therapeutic approach to gliomas.

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Authors

Contributions

Introduction (P.Y.W. and R.S.); Epidemiology (M. Brada and R.N.); Mechanisms/pathophysiology (G.R. and S.M.P.); Diagnosis, screening and prevention (K.A. and S.M.P.); Management (W.W. and M. Berger); Quality of life (M.R. and R.S.); Outlook (G.R., W.W. and M.W.); overview of Primer (M.W.).

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Correspondence to Michael Weller.

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Competing interests

M. Berger serves as a consultant for Ivivi Health Sciences. M. Brada served on advisory boards for Merck Serono, Roche and AbbVie. R.N. has received honoraria for lectures or advisory board participation, or sponsorship for meetings from MSD, Roche, Chugai, Nobelpharma, Eisai and Novocure. G.R. has received research grants from Roche and Merck, as well as honoraria for lectures or advisory boards from Roche and Amgen. R.S. has served on advisory boards for AbbVie, Actelion, Merck Serono, MSD, Novartis, Pfizer and Roche, and is or has been the coordinating investigator for sponsored clinical trials evaluating temozolomide (MSD), cilengitide (Merck Serono) and Tumour Treating Fields (Novocure). M.W. has received research grants from Acceleron, Actelion, Alpinia Institute, Bayer, Isarna, MSD, Merck Serono, Novocure, PIQUR and Roche, and honoraria for lectures or advisory board participation from AbbVie, Celldex, Isarna, MagForce, MSD, Merck Serono, Novartis, Novocure, Pfizer, Roche and Teva. P.Y.W. has received research grants from Amgen, AngioChem, AstraZeneca, Exelixis, Genentech/Roche, GlaxoSmithKline, Merck, Novartis, Sanofi-Aventis and Vascular Biogenics, and honoraria for lectures or advisory board participation from AbbVie, Celldex, Foundation Medicine, Genentech/Roche, Merck, Novartis, Vascular Biogenics, Midatech and Monteris. W.W. has received research grants from Apogenix, Boehringer Ingelheim, Eli Lilly, immatics, MSD and Roche, as well as honoraria for lectures or advisory board participation from MSD and Roche. W.W. is or has been the coordinating investigator for sponsored clinical trials evaluating APG101 (Apogenix), bevacizumab (Roche), galunisertib (Eli Lilly), temozolomide (MSD) and temsirolimus (Pfizer). S.M.P. and M.R. and K.A. declare no competing interests.

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Weller, M., Wick, W., Aldape, K. et al. Glioma. Nat Rev Dis Primers 1, 15017 (2015). https://doi.org/10.1038/nrdp.2015.17

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