Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-05T04:05:06.121Z Has data issue: false hasContentIssue false

Chapter 12 - Glioma

from Section 2 - Clinical Neurosurgical Diseases

Published online by Cambridge University Press:  04 January 2024

By
David M. Ashley  and
Low Justin T.
Edited by
Farhana Akter ,
Nigel Emptage ,
Florian Engert  and
Mitchel S. Berger
Farhana Akter
Affiliation:
Harvard University, Massachusetts
Nigel Emptage
Affiliation:
University of Oxford
Florian Engert
Affiliation:
Harvard University, Massachusetts
Mitchel S. Berger
Affiliation:
University of California, San Francisco
Get access

Summary

In this chapter we survey the clinical and pathophysiologic principles of gliomas, the primary tumors of the central nervous system. We describe the histologic and clinical features of the main glioma subtypes, including diffuse astrocytic and oligodendroglial gliomas, as well as circumscribed gliomas such as pilocytic astrocytoma and ependymoma. In 2016 the World Health Organization incorporated genetic markers into the diagnostic criteria for gliomas. We discuss the key molecular discoveries that underlie these diagnostic changes, including IDH mutations and 1p/19q codeletion in diffuse gliomas, and the RELA fusion in ependymomas. We provide an overview of the molecular processes and pathways fundamental to gliomagenesis, including disruptions in cell cycle checkpoints, growth factor signaling, telomere maintenance, and epigenetic regulation. Finally, we highlight the physiologic mechanisms of important clinical sequelae of gliomas, including cerebral edema, immune dysregulation, and systemic hypercoagulability.

Type
Chapter
Information
Neuroscience for Neurosurgeons , pp. 184 - 192
Publisher: Cambridge University Press
Print publication year: 2024

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alcantara Llaguno, S, Chen, J, Kwon, C-H, et al. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 2009;15(1):45–56. https://doi.org/10.1016/j.ccr.2008.12.006.Google Scholar
Arita, H, Narita, Y, Fukushima, S, et al. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol 2013;126(2):267–76. https://doi.org/10.1007/s00401-013-1141-6.CrossRefGoogle ScholarPubMed
Bao, S, Wu, Q, McLendon, RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006;444(7120):756–60. https://doi.org/10.1038/nature05236.Google Scholar
Baron, JA, Gridley, G, Weiderpass, E, Nyrén, O, Linet, M. Venous thromboembolism and cancer. Lancet 1998;351(9109):1077–80. https://doi.org/10.1016/S0140-6736(97)10018-6.CrossRefGoogle ScholarPubMed
Cairncross, G, Wang, M, Shaw, E, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 2013;31(3):337–43. https://doi.org/10.1200/JCO.2012.43.2674.Google Scholar
Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455(7216):1061–8. https://doi.org/10.1038/nature07385.Google Scholar
Capper, D, Jones, DTW, Sill, M, et al. DNA methylation-based classification of central nervous system tumors. Nature 2018;555(7697):469–74. https://doi.org/10.1038/nature26000.Google Scholar
Ceccarelli, M, Barthel, FP, Malta, TM, et al. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell 2016;164(3):550–63. https://doi.org/10.1016/j.cell.2015.12.028.Google Scholar
Chen, H, Judkins, J, Thomas, C, et al. Mutant IDH1 and seizures in patients with glioma. Neurology 2017;88(19):1805–13. https://doi.org/10.1212/WNL.0000000000003911.CrossRefGoogle ScholarPubMed
Dang, L, White, DW, Gross, S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462(7274):739–44. https://doi.org/10.1038/nature08617.Google Scholar
Dong, X, Noorbakhsh, A, Hirshman, BR, et al. Survival trends of grade I, II, and III astrocytoma patients and associated clinical practice patterns between 1999 and 2010: a SEER-based analysis. Neurooncol Pract 2016;3(1):29–38. https://doi.org/10.1093/nop/npv016.Google Scholar
Fecci, PE, Sampson, JH. The current state of immunotherapy for gliomas: an eye toward the future. J Neurosurg 2019;131(3):657–66. https://doi.org/10.3171/2019.5.JNS181762.Google Scholar
Figueroa, ME, Abdel-Wahab, O, Lu, C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010;18(6):553–67. https://doi.org/10.1016/j.ccr.2010.11.015.Google Scholar
Flavahan, WA, Drier, Y, Liau, BB, et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 2016;529(7584):110–4. https://doi.org/10.1038/nature16490.CrossRefGoogle ScholarPubMed
Fontebasso, AM, Liu, X-Y, Sturm, D, Jabado, N. Chromatin remodeling defects in pediatric and young adult glioblastoma: a tale of a variant histone 3 tail. Brain Pathol 2013;23(2):210–6. https://doi.org/10.1111/bpa.12023.Google Scholar
Galli, R, Binda, E, Orfanelli, U, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 2004;64(19):7011–21. https://doi.org/10.1158/0008-5472.CAN-04-1364.Google Scholar
Gatta, G, Botta, L, Rossi, S, et al. Childhood cancer survival in Europe 1999–2007: results of EUROCARE-5 – a population-based study. Lancet Oncol 2014;15(1):35–47. https://doi.org/10.1016/S1470-2045(13)70548-5.CrossRefGoogle ScholarPubMed
Gorovets, D, Kannan, K, Shen, R, et al. IDH mutation and neuroglial developmental features define clinically distinct subclasses of lower grade diffuse astrocytic glioma. Clin Cancer Res 2012;18(9):2490–501. https://doi.org/10.1158/1078-0432.CCR-11-2977.Google Scholar
Grabowski, MM, Sankey, EW, Ryan, KJ, et al. Immune suppression in gliomas. J Neurooncol 2021;151(1):3–12. https://doi.org/10.1007/s11060-020-03483-y.Google Scholar
Gusyatiner, O, Hegi, ME. Glioma epigenetics: from subclassification to novel treatment options. Semin Cancer Biol 2018;51:50–8. https://doi.org/10.1016/j.semcancer.2017.11.010.CrossRefGoogle ScholarPubMed
Heaphy, CM, de Wilde, RF, Jiao, Y, et al. Altered telomeres in tumors with ATRX and DAXX mutations. Science 2011;333(6041):425. https://doi.org/10.1126/science.1207313.CrossRefGoogle ScholarPubMed
Hegi, ME, Diserens, A-C, Gorlia, T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352(10):997–1003. https://doi.org/10.1056/NEJMoa043331.Google Scholar
Horsted, F, West, J, Grainge, MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012;9(7):e1001275. https://doi.org/10.1371/journal.pmed.1001275.Google Scholar
Jones, DTW, Hutter, B, Jäger, N, et al. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat Genet 2013;45(8):927–32. https://doi.org/10.1038/ng.2682.Google Scholar
Jones, DTW, Kocialkowski, S, Liu, L, et al. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 2008;68(21):8673–7. https://doi.org/10.1158/0008-5472.CAN-08-2097.Google Scholar
Kreth, S, Thon, N, Kreth, FW. Epigenetics in human gliomas. Cancer Lett 2014;342(2):185–92. https://doi.org/10.1016/j.canlet.2012.04.008.Google Scholar
Kroonen, J, Nassen, J, Boulanger, Y-G, et al. Human glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection. Int J Cancer 2011;129(3):574–85. https://doi.org/10.1002/ijc.25709.Google Scholar
Lee, JH, Lee, JE, Kahng, JY, et al. Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature 2018;560(7717):243–7. https://doi.org/10.1038/s41586-018-0389-3.Google Scholar
Liu, G, Yuan, X, Zeng, Z, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 2006;5:67. https://doi.org/10.1186/1476-4598-5-67.Google Scholar
Liubinas, SV, D’Abaco, GM, Moffat, BM, et al. IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas. Epilepsia 2014;55(9):1438–43. https://doi.org/10.1111/epi.12662.Google Scholar
Louis, DN, Perry, A, Reifenberger, G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131(6):803–20. https://doi.org/10.1007/s00401-016-1545-1.CrossRefGoogle ScholarPubMed
Mandoj, C, Tomao, L, Conti, L. Coagulation in brain tumors: biological basis and clinical implications. Front Neurol 2019;10:181. https://doi.org/10.3389/fneur.2019.00181.Google Scholar
Matarredona, ER, Pastor, AM. Neural stem cells of the subventricular zone as the origin of human glioblastoma stem cells. Therapeutic implications. Front Oncol 2019;9:779. https://doi.org/10.3389/fonc.2019.00779.Google Scholar
Nadi, M, Rutka, J. Molecular markers and pathways in brain tumorigenesis. In Bernstein, M, Berger, MS (Eds.), Neuro-Oncology: The Essentials, 3rd ed. Thieme Verlag, 2015, pp. 35–46.Google Scholar
Ohgaki, H, Kleihues, P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 2005;64(6):479–89. https://doi.org/10.1093/jnen/64.6.479.Google Scholar
Olson, JD, Riedel, E, DeAngelis, LM. Long-term outcome of low-grade oligodendroglioma and mixed glioma. Neurology 2000;54(7):1442–8. https://doi.org/10.1212/wnl.54.7.1442.Google Scholar
Ostrom, QT, Gittleman, H, Liao, P, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 2014;16(Suppl 4):iv1–63. https://doi.org/10.1093/neuonc/nou223.Google Scholar
Pallud, J, Capelle, L, Huberfeld, G. Tumoral epileptogenicity: how does it happen? Epilepsia 2013;54(Suppl 9):30–4. https://doi.org/10.1111/epi.12440.Google Scholar
Papadopoulos, MC, Saadoun, S, Binder, DK, Manley, GT, Krishna, S, Verkman, AS. Molecular mechanisms of brain tumor edema. Neuroscience 2004;129(4):1011–20. https://doi.org/10.1016/j.neuroscience.2004.05.044.Google Scholar
Parker, M, Mohankumar, KM, Punchihewa, C, et al. C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma. Nature 2014;506(7489):451–5. https://doi.org/10.1038/nature13109.CrossRefGoogle ScholarPubMed
Peng, Z, Liu, C, Wu, M. New insights into long noncoding RNAs and their roles in glioma. Mol Cancer 2018;17(1):61. https://doi.org/10.1186/s12943-018-0812-2.Google Scholar
Portela, A, Esteller, M. Epigenetic modifications and human disease. Nat Biotechnol 2010;28(10):1057–68. https://doi.org/10.1038/nbt.1685.Google Scholar
Reifenberger, G, Louis, DN. Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003;62(2):111–26. https://doi.org/10.1093/jnen/62.2.111.Google Scholar
Reifenberger, J, Ring, GU, Gies, U, et al. Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression. J Neuropathol Exp Neurol 1996;55(7):822–31. https://doi.org/10.1097/00005072-199607000-00007.Google Scholar
Reuss, DE, Mamatjan, Y, Schrimpf, D, et al. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. Acta Neuropathol 2015;129(6):867–73. https://doi.org/10.1007/s00401-015-1438-8.Google Scholar
Ropper, AH, Samuels, MA, Klein, JP, Prasad, S. Intracranial neoplasms and paraneoplastic disorders. In: Adams and Victor’s Principles of Neurology, 11th ed. McGraw-Hill Education, 2019.Google Scholar
Samudra, N, Zacharias, T, Plitt, A, Lega, B, Pan, E. Seizures in glioma patients: an overview of incidence, etiology, and therapies. J Neurol Sci 2019;404:80–5. https://doi.org/10.1016/j.jns.2019.07.026.Google Scholar
Sanai, N, Tramontin, AD, Quiñones-Hinojosa, A, et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 2004;427(6976):740–4. https://doi.org/10.1038/nature02301.Google Scholar
Sanson, M, Marie, Y, Paris, S, et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009;27(25):4150–4. https://doi.org/10.1200/JCO.2009.21.9832.Google Scholar
Schwartzentruber, J, Korshunov, A, Liu, X-Y, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 2012;482(7384):226–31. https://doi.org/10.1038/nature10833.CrossRefGoogle ScholarPubMed
Shay, JW, Bacchetti, S. A survey of telomerase activity in human cancer. Eur J Cancer 1997;33(5):787–91. https://doi.org/10.1016/S0959-8049(97)00062-2.Google Scholar
Shi, J, Dong, B, Cao, J, et al. Long non-coding RNA in glioma: signaling pathways. Oncotarget 2017;8(16):27582–92. https://doi.org/10.18632/oncotarget.15175.Google Scholar
Singh, SK, Hawkins, C, Clarke, ID, et al. Identification of human brain tumor initiating cells. Nature 2004;432(7015):396–401. https://doi.org/10.1038/nature03128.Google Scholar
Stephens, PJ, Greenman, CD, Fu, B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 2011;144(1):27–40. https://doi.org/10.1016/j.cell.2010.11.055.Google Scholar
Stummer, W. Mechanisms of tumor-related brain edema. Neurosurg Focus 2007;22(5):E8. https://doi.org/10.3171/foc.2007.22.5.9.Google Scholar
Sullivan, JP, Nahed, BV, Madden, MW, et al. Brain tumor cells in circulation are enriched for mesenchymal gene expression. Cancer Discov 2014;4(11):1299–309. https://doi.org/10.1158/2159-8290.CD-14-0471.CrossRefGoogle ScholarPubMed
Takano, T, Lin, JH, Arcuino, G, Gao, Q, Yang, J, Nedergaard, M. Glutamate release promotes growth of malignant gliomas. Nat Med 2001;7(9):1010–5. https://doi.org/10.1038/nm0901-1010.Google Scholar
Turcan, S, Rohle, D, Goenka, A, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012;483(7390):479–83. https://doi.org/10.1038/nature10866.Google Scholar
Verhaak, RGW, Hoadley, KA, Purdom, E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010;17(1):98–110. https://doi.org/10.1016/j.ccr.2009.12.020.Google Scholar
Walker, A, West, J, Card, T, Crooks, C, Grainge, M. Rate of venous thromboembolism by cancer type compared to the general population using multiple linked databases. Thrombosis Res 2012;129:S155–6.Google Scholar
Watanabe, K, Sato, K, Biernat, W, et al. Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clin Cancer Res 1997;3(4):523–30.Google Scholar
Wikstrand, CJ, Reist, CJ, Archer, GE, Zalutsky, MR, Bigner, DD. The class III variant of the epidermal growth factor receptor (EGFRvIII): characterization and utilization as an immunotherapeutic target. J Neurovirol 1998;4(2):148–58. https://doi.org/10.3109/13550289809114515.Google Scholar
Wu, G, Broniscer, A, McEachron, TA, et al. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 2012;44(3):251–3. https://doi.org/10.1038/ng.1102.Google Scholar
Yan, H, Parsons, DW, Jin, G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009;360(8):765–73. https://doi.org/10.1056/NEJMoa0808710.Google Scholar
Zhang, J, Wu, G, Miller, CP, et al. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet 2013;45(6):602–12. https://doi.org/10.1038/ng.2611.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×