Skip to main content
SpringerLink
Log in

The Epigenetics of Brain Tumors: Fundamental Aspects of Epigenetics in Glioma

  • Chapter
  • First Online:
Cancer Epigenetics

Part of the book series: Epigenetics and Human Health ((EHH,volume 11))

  • 196 Accesses

Abstract

A brain tumor is an abnormal growth of heterogeneous cells around the central nervous system and spinal cord. It is seen in different types and frequencies in children and adults. Today, surgery, radiotherapy, and chemotherapy are common treatment approaches. Comprehensive molecular profiling has dramatically changed the diagnostic neuropathology of brain tumors. Diffuse gliomas, the most common and fatal brain tumor variants, are now classified by highly repetitive biomarkers rather than histomorphological features. Many critical molecular changes that drive glioma classification involve fundamental epigenetic dysregulation, an area not previously thought to play important roles in glioma pathogenesis. Considering tumor heterogeneity in the classification of brain tumors, molecular markers provide more accurate results in diagnosis, prognosis, and selection of treatment approaches. Recently, epigenetic changes have received increasing attention as they aid in understanding the mechanism of chromatin-mediated disease. Epigenetic modification alters the chromatin structure, which affects the docking site of many drugs that cause chemoresistance in cancer therapy. This chapter will review the main epigenetic changes underlying malignant gliomas and their possible mechanisms of action, based on the WHO 2021 classification.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

5caC:

5-Carboxylcytosine

5fC:

5-Formylcytosine

APNG:

Alkylpurine-DNA-N-glycosylase

ASIR:

Age-standardized incidence rate

ASMR:

Age-standardized mortality rate

ATPase:

Adenosine triphosphatase

CGI:

CpG islands

CNS:

Central nervous system

CTCF:

CCCTC-binding factor

DIPGs :

Diffuse intrinsic pontine gliomas

DNMTs:

DNA methyltransferases

G-CIMP:

Glioma CpG island methylator phenotype

HATs:

Histone acetyltransferases

HDACi:

HDAC inhibitors

HDACs:

Histone deacetylases

mRNAs:

Messenger RNAs

NADP(+):

Nicotinamide adenine dinucleotide phosphate

ncRNAs:

Noncoding RNAs

TCGA :

The Cancer Genome Atlas

TMZ:

Temozolomide

α-KG:

α-Ketoglutarate

References

  • Akers JC, Hua W, Li H, Ramakrishnan V, Yang Z, Quan K, Zhu W, Li J, Figueroa J, Hirshman BR, Miller B, Piccioni D, Ringel F, Komotar R, Messer K, Galasko DR, Hochberg F, Mao Y, Carter BS, Chen CC (2017 Jun 1) A cerebrospinal fluid microRNA signature as biomarker for glioblastoma. Oncotarget 8(40):68769–68779. https://doi.org/10.18632/oncotarget.18332. PMID: 28978155; PMCID: PMC5620295.

  • Aldera AP, Govender D (2022) Gene of the month: H3F3A and H3F3B. J Clin Pathol 75:1–4

    Article  CAS  PubMed  Google Scholar 

  • An J, Rao A, Ko M (2017) TET family dioxygenases and DNA demethylation in stem cells and cancers. Exp Mol Med 49:e323–e323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arslantas A, Artan S, Öner Ü, Müslümanoğlu H, Durmaz R, Cosan E, Atasoy MA, Başaran N, Tel E (2004) The importance of genomic copy number changes in the prognosis of glioblastoma multiforme. Neurosurg Rev 27:58–64

    Article  PubMed  Google Scholar 

  • Arslantas A, Artan S, Öner Ü, Müslümanoglu MH, Özdemir M, Durmaz R, Arslantas D, Vural M, Cosan E, Atasoy MA (2007) Genomic alterations in low-grade, anaplastic astrocytomas and glioblastomas. Pathol Oncol Res 13:39–46

    Article  CAS  PubMed  Google Scholar 

  • Asmar F, Søgaard A, Grønbæk K (2015) DNA methylation and hydroxymethylation in cancer. Elsevier, Epigenetic Cancer Therapy

    Book  Google Scholar 

  • Black JC, Van Rechem C, Whetstine JR (2012) Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell 48:491–507

    Article  CAS  PubMed  Google Scholar 

  • Blakey CA, Litt MD (2015) Histone modifications—models and mechanisms. In: Epigenetic gene expression and regulation. Elsevier

    Google Scholar 

  • Brennan CW, Verhaak RG, Mckenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, BERMAN, S. H. (2013) The somatic genomic landscape of glioblastoma. Cell 155:462–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broniscer A, Gajjar A (2004) Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist 9(2):197–206. https://doi.org/10.1634/theoncologist.9-2-197

    Article  PubMed  Google Scholar 

  • Carella A, Tejedor JR, García MG, Urdinguio RG, Bayón GF, Sierra M, López V, García-Toraño E, Santamarina-Ojeda P, Pérez RF (2020) Epigenetic downregulation of TET3 reduces genome-wide 5hmC levels and promotes glioblastoma tumorigenesis. Int J Cancer 146:373–387

    Article  CAS  PubMed  Google Scholar 

  • Cavalli G, Heard E (2019) Advances in epigenetics link genetics to the environment and disease. Nature 571:489–499

    Article  CAS  PubMed  Google Scholar 

  • Ceccarelli M, Barthel FP, Malta TM, Sabedot TS, Salama SR, Murray BA, Morozova O, Newton Y, Radenbaugh A, Pagnotta SM (2016) Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell 164:550–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Z, Shi X, Guo L, Li Y, Luo M, He J (2017) Decreased 5-hydroxymethylcytosine levels correlate with cancer progression and poor survival: a systematic review and meta-analysis. Oncotarget 8:1944

    Article  PubMed  Google Scholar 

  • Cheng Y, He C, Wang M, Ma X, Mo F, Yang S, Han J, Wei X (2019) Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther 4:1–39

    Google Scholar 

  • Dabrowski J, Michal, Wojtas B (2019) Global DNA methylation patterns in human gliomas and their interplay with other epigenetic modifications. Int J Mol Sci 20:3478

    Article  CAS  Google Scholar 

  • Dang L, Yen K, Attar E (2016) IDH mutations in cancer and progress toward development of targeted therapeutics. Ann Oncol 27:599–608

    Article  CAS  PubMed  Google Scholar 

  • Dawson MA (2017) The cancer epigenome: concepts, challenges, and therapeutic opportunities. Science 355:1147–1152

    Article  CAS  PubMed  Google Scholar 

  • Dharmaiah S, Huse JT (2022) The epigenetic dysfunction underlying malignant glioma pathogenesis. Lab Investig 102:1–9

    Article  Google Scholar 

  • Duchatel RJ, Jackson ER, Alvaro F, Nixon B, Hondermarck H, Dun MD (2019) Signal transduction in diffuse intrinsic pontine glioma. Proteomics 19:1800479

    Article  CAS  Google Scholar 

  • Duke ES, Packer RJ (2020) Update on pediatric brain tumors: the molecular era and neuro-immunologic beginnings. Curr Neurol Neurosci Rep 20:1–8

    Article  Google Scholar 

  • Ehrlich M (2019) DNA hypermethylation in disease: mechanisms and clinical relevance. Epigenetics 14:1141–1163

    Article  PubMed  PubMed Central  Google Scholar 

  • Fan Y, Zhang X, Gao C, Jiang S, Wu H, Liu Z, Dou T (2022) Burden and trends of brain and central nervous system cancer from 1990 to 2019 at the global, regional, and country levels. Arch Publ Health 80:1–14

    Article  Google Scholar 

  • Fang J, Huang Y, Mao G, Yang S, Rennert G, Gu L, Li H, Li G-M (2018) Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3–MutSα interaction. Proc Natl Acad Sci 115:9598–9603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92

    Article  CAS  PubMed  Google Scholar 

  • Ferrer AI, Trinidad JR, Sandiford O, Etchegaray J-P, Rameshwar P (2020) Epigenetic dynamics in cancer stem cell dormancy. Cancer Metastasis Rev 39:721–738

    Article  PubMed  Google Scholar 

  • Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS, Stemmer-Rachamimov AO, Suvà ML, Bernstein BE (2016) Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529(7584):110–114. https://doi.org/10.1038/nature16490

    Article  CAS  PubMed  Google Scholar 

  • Gibbons RJ, Picketts DJ, Villard L, Higgs DR (1995) Mutations in a putative global transcriptional regulator cause X-linked mental retardation with α-thalassemia (ATR-X syndrome). Cell 80:837–845

    Article  CAS  PubMed  Google Scholar 

  • Globisch D, Münzel M, Müller M, Michalakis S, Wagner M, Koch S, Brückl T, Biel M, Carell T (2010) Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLoS One 5:e15367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greenberg MV, Bourćhis D (2019) The diverse roles of DNA methylation in mammalian development and disease. Nat Rev Mol Cell Biol 20:590–607

    Article  CAS  PubMed  Google Scholar 

  • Greuter L, Guzman R, Soleman J (2021) Typical pediatric brain tumors occurring in adults—differences in management and outcome. Biomedicine 9:356

    CAS  Google Scholar 

  • Gritsch S, Batchelor TT, Gonzalez Castro LN (2022) Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system. Cancer 128:47–58

    Article  PubMed  Google Scholar 

  • Guo M, Peng Y, Gao A, Du C, Herman JG (2019) Epigenetic heterogeneity in cancer. Biomarker Res 7:1–19

    Article  Google Scholar 

  • Gupta R, Flanagan S, Li CC, Lee M, Shivalingham B, Maleki S, Wheeler HR, Buckland ME (2013) Expanding the spectrum of IDH1 mutations in gliomas. Modern pathology: an official journal of the United States and Canadian Academy of Pathology. Inc 26(5):619–625. https://doi.org/10.1038/modpathol.2012.210

  • Gusyatiner O, Hegi ME (2018) Glioma epigenetics: from subclassification to novel treatment options. In: Seminars in cancer biology. Elsevier, pp 50–58

    Google Scholar 

  • Hahn MA, Qiu R, Wu X, Li AX, Zhang H, Wang J, Jui J, Jin S-G, Jiang Y, Pfeifer GP (2013) Dynamics of 5-hydroxymethylcytosine and chromatin marks in mammalian neurogenesis. Cell Rep 3:291–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han S, Liu Y, Cai SJ, Qian M, Ding J, Larion M, Gilbert MR, Yang C (2020) IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer 122:1580–1589

    Article  PubMed  PubMed Central  Google Scholar 

  • Hegi ME, Genbrugge E, Gorlia T, Stupp R, Gilbert MR, Chinot OL, Nabors LB, Jones G, Van Criekinge W, Straub J (2019) MGMT promoter methylation cutoff with safety margin for selecting glioblastoma patients into trials omitting Temozolomide: A pooled analysis of four clinical TrialsMGMT safety margin for glioblastoma. Clin Cancer Res 25:1809–1816

    Article  PubMed  Google Scholar 

  • Iurlaro M, Ficz G, Oxley D, Raiber E-A, Bachman M, Booth MJ, Andrews S, Balasubramanian S, Reik W (2013) A screen for hydroxymethylcytosine and formylcytosine binding proteins suggests functions in transcription and chromatin regulation. Genome Biol 14:1–11

    Article  Google Scholar 

  • Kalkan R, Atli Eİ, Özdemir M, Çiftçi E, Aydin HE, Artan S, Arslantaş A (2015) IDH1 mutations is prognostic marker for primary glioblastoma multiforme but MGMT hypermethylation is not prognostic for primary glioblastoma multiforme. Gene 554:81–86

    Article  CAS  PubMed  Google Scholar 

  • Kamińska K, Nalejska E, Kubiak M, Wojtysiak J, Żołna Ł, Kowalewski J, Lewandowska MA (2019) Prognostic and predictive epigenetic biomarkers in oncology. Mol Diagn Ther 23: 83–95

    Google Scholar 

  • Kheder ES, Hong DS (2018) Emerging targeted therapy for tumors with NTRK fusion ProteinsNovel targeted therapy for NTRK-rearranged tumors. Clin Cancer Res 24:5807–5814

    Article  CAS  PubMed  Google Scholar 

  • Ko M, An J, Pastor WA, Koralov SB, Rajewsky K, Rao A (2015) TET proteins and 5-methylcytosine oxidation in hematological cancers. Immunol Rev 263:6–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koivunen P, Laukka T (2018) The TET enzymes. Cell Mol Life Sci 75:1339–1348

    Article  CAS  PubMed  Google Scholar 

  • Kristensen B, Priesterbach-Ackley L, Petersen J, Wesseling P (2019) Molecular pathology of tumors of the central nervous system. Ann Oncol 30:1265–1278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kukreja L, Li CJ, Ezhilan S, Iyer VR, Kuo JS (2021) Emerging epigenetic therapies for brain tumors. NeuroMolecular Med 24:1–9

    Google Scholar 

  • La Madrid AM, Kieran MW (2018) Epigenetics in clinical management of children and adolescents with brain tumors. Curr Cancer Drug Targets 18:57–64

    Article  PubMed  Google Scholar 

  • Le Rhun E, Weller M (2020) Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours. ESMO Open 5:e001034

    Article  PubMed  PubMed Central  Google Scholar 

  • Leibetseder A, Preusser M, Berghoff AS (2022) New approaches with precision medicine in adult brain tumors. Cancers 14:712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu D, Yang T, Ma W, Wang Y (2022) Clinical strategies to manage adult glioblastoma patients without MGMT hypermethylation. J Cancer 13:354

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Lang F, Chou F-J, Zaghloul KA, Yang C (2020) Isocitrate dehydrogenase mutations in glioma: genetics, biochemistry, and clinical indications. Biomedicine 8:294

    CAS  Google Scholar 

  • Losman J-A, Kaelin WG (2013) What a difference a hydroxyl makes: mutant IDH,(R)-2-hydroxyglutarate, and cancer. Genes Dev 27:836–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Louis DN, Perry A, Reifenberger G, Von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820

    Article  PubMed  Google Scholar 

  • Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng H, Pfister SM, Reifenberger G (2021) The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-Oncology 23:1231–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lowe BR, Maxham LA, Hamey JJ, Wilkins MR, Partridge JF (2019) Histone H3 mutations: an updated view of their role in chromatin deregulation and cancer. Cancers 11:660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y, Chan Y-T, Tan H-Y, Li S, Wang N, Feng Y (2020) Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol Cancer 19:1–16

    Article  CAS  Google Scholar 

  • Malta TM, De Souza CF, Sabedot TS, Silva TC, Mosella MS, Kalkanis SN, Snyder J, Castro AVB, Noushmehr H (2018) Glioma CpG Island methylator phenotype (G-CIMP): biological and clinical implications. Neuro-Oncology 20:608–620

    Article  CAS  PubMed  Google Scholar 

  • Mancarella D, Plass C (2021) Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation. Genome Med 13:1–12

    Article  Google Scholar 

  • Mcnamara C, Mankad K, Thust S, Dixon L, Limback-Stanic C, D’arco F, Jacques TS, Löbel U (2022) 2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist. Neuroradiology 64:1–32

    Article  Google Scholar 

  • Miklja Z, Pasternak A, Stallard S, Nicolaides T, Kline-Nunnally C, Cole B, Beroukhim R, Bandopadhayay P, Chi S, Ramkissoon SH (2019) Molecular profiling and targeted therapy in pediatric gliomas: review and consensus recommendations. Neuro-Oncology 21:968–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller KD, Ostrom QT, Kruchko C, Patil N, Tihan T, Cioffi G, Fuchs HE, Waite KA, Jemal A, Siegel RL (2021) Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin 71:381–406

    Article  PubMed  Google Scholar 

  • Molinaro AM, Taylor JW, Wiencke JK, Wrensch MR (2019) Genetic and molecular epidemiology of adult diffuse glioma. Nat Rev Neurol 15:405–417

    Article  PubMed  PubMed Central  Google Scholar 

  • Münzel M, Globisch D, Brückl T, Wagner M, Welzmiller V, Michalakis S, Müller M, Biel M, Carell T (2010) Quantification of the sixth DNA base hydroxymethylcytosine in the brain. Angew Chem Int Ed 49:5375–5377

    Article  Google Scholar 

  • Mur P, Rodríguez de Lope Á, Díaz-Crespo FJ, Hernández-Iglesias T, Ribalta T, Fiaño C, García JF, Rey JA, Mollejo M, Meléndez B (2015) Impact on prognosis of the regional distribution of MGMT methylation with respect to the CpG Island methylator phenotype and age in glioma patients. J Neuro-Oncol 122:441–450

    Article  CAS  Google Scholar 

  • Nandakumar P, Mansouri A, DAS, S. (2017) The role of ATRX in glioma biology. Front Oncol 7:236

    Article  PubMed  PubMed Central  Google Scholar 

  • Network CGAR (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498

    Article  Google Scholar 

  • Nishiyama A, Nakanishi M (2021) Navigating the DNA methylation landscape of cancer. Trends Genet 37:1012–1027

    Article  CAS  PubMed  Google Scholar 

  • Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP (2010) Identification of a CpG Island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orr BA, Haffner MC, Nelson WG, Yegnasubramanian S, Eberhart CG (2012) Decreased 5-hydroxymethylcytosine is associated with neural progenitor phenotype in normal brain and shorter survival in malignant glioma. PLoS One 7:e41036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM (2014) The epidemiology of glioma in adults: a “state of the science” review. Neuro-Oncology 16:896–913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS (2019) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016. Neuro-Oncology 21:v1–v100

    Article  PubMed  PubMed Central  Google Scholar 

  • Özdemir Sİ, Şimşek AY, Emel Ü (2022) NTRK somatic fusions and tumor agnostic treatment in pediatric cancers. J Contemp Med:12(6):1019-1024.

    Google Scholar 

  • Patel AP, Fisher JL, Nichols E, Abd-Allah F, Abdela J, Abdelalim A, Abraha HN, Agius D, Alahdab F, Alam T (2019) Global, regional, and national burden of brain and other CNS cancer, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol 18:376–393

    Article  Google Scholar 

  • Patil N, Abba ML, Zhou C, Chang S, Gaiser T, Leupold JH, Allgayer H (2021) Changes in methylation across structural and MicroRNA genes relevant for progression and metastasis in colorectal cancer. Cancers 13:5951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perez E, Capper D (2020) Invited review: DNA methylation-based classification of paediatric brain tumours. Neuropathol Appl Neurobiol 46:28–47

    Article  CAS  PubMed  Google Scholar 

  • Pfeifer GP, Xiong W, Hahn MA, Jin S-G (2014) The role of 5-hydroxymethylcytosine in human cancer. Cell Tissue Res 356:631–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Puduvalli VK (2014) Epigenetic changes in gliomas. In: Glioma cell biology. Springer

    Google Scholar 

  • Qin T, Mullan B, Ravindran R, Messinger D, Siada R, Cummings JR, Harris M, Muruganand A, Pyaram K, Miklja Z (2022) ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization. Cell Rep 38:110216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raviraj R, Nagaraja SS, Selvakumar I, Mohan S, Nagarajan D (2020) The epigenetics of brain tumors and its modulation during radiation: A review. Life Sci 256:117974

    Article  CAS  PubMed  Google Scholar 

  • Romani M, Pistillo MP, Banelli B (2018) Epigenetic targeting of glioblastoma. Front Oncol 8:448

    Article  PubMed  PubMed Central  Google Scholar 

  • Ross JL, Velazquez Vega J, Plant A, Macdonald TJ, Becher OJ, Hambardzumyan D (2021) Tumour immune landscape of paediatric high-grade gliomas. Brain 144:2594–2609

    Article  PubMed  PubMed Central  Google Scholar 

  • Roth P, Wischhusen J, Happold C, Chandran PA, Hofer S, Eisele G, Weller M, Keller A (2011) A specific miRNA signature in the peripheral blood of glioblastoma patients. J Neurochem 118(3):449–457. https://doi.org/10.1111/j.1471-4159.2011.07307.x

    Article  CAS  PubMed  Google Scholar 

  • Scourzic L, Mouly E, Bernard OA (2015) TET proteins and the control of cytosine demethylation in cancer. Genome Med 7:1–16

    Article  Google Scholar 

  • Sharma S, Aazmi O (2019) Basics of epigenetics: it is more than simple changes in sequence that govern gene expression. Elsevier, Prognostic Epigenetics

    Google Scholar 

  • Shoaib M, Walter D, Gillespie PJ, Izard F, Fahrenkrog B, Lleres D, Lerdrup M, Johansen JV, Hansen K, Julien E (2018) Histone H4K20 methylation mediated chromatin compaction threshold ensures genome integrity by limiting DNA replication licensing. Nat Commun 9:1–11

    Article  CAS  Google Scholar 

  • Siegal T, Charbit H, Paldor I, Zelikovitch B, Canello T, Benis A, Wong ML, Morokoff A, Kaye AH, Lavon I (2016) Dynamics of circulating hypoxia-mediated miRNAs and tumor response in patients with high-grade glioma treated with bevacizumab. J Neurosurg 125(4):1008–1015. https://doi.org/10.3171/2015.8.JNS15437

    Article  CAS  PubMed  Google Scholar 

  • Śledzińska P, Bebyn MG, Furtak J, Kowalewski J, Lewandowska MA (2021) Prognostic and predictive biomarkers in gliomas. Int J Mol Sci 22:10373

    Article  PubMed  PubMed Central  Google Scholar 

  • Stanton BZ, Hodges C, Crabtree GR, Zhao K (2017) A general non-radioactive ATPase assay for chromatin remodeling complexes. Curr Protocols Chem Biol 9:1–10

    Article  CAS  Google Scholar 

  • Sun L, Zhang H, Gao P (2021) Metabolic reprogramming and epigenetic modifications on the path to cancer. Protein Cell:1–43

    Google Scholar 

  • Takai H, Masuda K, Sato T, Sakaguchi Y, Suzuki T, Suzuki T, Koyama-Nasu R, Nasu-Nishimura Y, Katou Y, Ogawa H (2014) 5-Hydroxymethylcytosine plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex. Cell Rep 9:48–60

    Article  CAS  PubMed  Google Scholar 

  • Tesileanu CMS, Dirven L, Wijnenga MM, Koekkoek JA, Vincent AJ, Dubbink HJ, Atmodimedjo PN, Kros JM, Van Duinen SG, Smits M (2020) Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria. Neuro-Oncology 22:515–523

    Article  CAS  PubMed  Google Scholar 

  • Thienpont B, Steinbacher J, Zhao H, D’anna F, Kuchnio A, Ploumakis A, Ghesquière B, Van Dyck L, Boeckx B, Schoonjans L (2016) Tumour hypoxia causes DNA hypermethylation by reducing TET activity. Nature 537:63–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tian S, Wang J, Zhang F, Wang D (2022) Comparative analysis of microRNA binding site distribution and microRNA-mediated gene expression repression of oncogenes and tumor suppressor genes. Gene 13:481

    Article  CAS  Google Scholar 

  • Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa J-PJ (1999) CpG Island methylator phenotype in colorectal cancer. Proc Natl Acad Sci 96:8681–8686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, Campos C, Fabius AW, Lu C, Ward PS (2012) IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483:479–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uddin MS, Al Mamun A, Alghamdi BS, Tewari D, Jeandet P, Sarwar MS, Ashraf GM (2022) Epigenetics of glioblastoma multiforme: from molecular mechanisms to therapeutic approaches. In: Seminars in cancer biology. Elsevier

    Google Scholar 

  • Valle-García D, Qadeer ZA, Mchugh DS, Ghiraldini FG, Chowdhury AH, Hasson D, Dyer MA, Recillas-Targa F, Bernstein E (2016) ATRX binds to atypical chromatin domains at the 3′ exons of zinc finger genes to preserve H3K9me3 enrichment. Epigenetics 11:398–414

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Damme M, Crompot E, Meuleman N, Maerevoet M, Mineur P, Bron D, Lagneaux L, Stamatopoulos B (2016) Characterization of TET and IDH gene expression in chronic lymphocytic leukemia: comparison with normal B cells and prognostic significance. Clin Epigenetics 8:1–11

    Google Scholar 

  • Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waitkus MS, Diplas BH, Yan H (2015) Isocitrate dehydrogenase mutations in gliomas. Neuro-Oncology 18:16–26

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang J, Che F, Zhang J (2019) Cell-free microRNAs as non-invasive biomarkers in glioma: a diagnostic meta-analysis. Int J Biol Markers 34(3):232–242. https://doi.org/10.1177/1724600819840033

    Article  CAS  PubMed  Google Scholar 

  • Wiles ET, Selker EU (2017) H3K27 methylation: a promiscuous repressive chromatin mark. Curr Opin Genet Dev 43:31–37

    Article  CAS  PubMed  Google Scholar 

  • Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim S-H, Ito S, Yang C, Wang P, Xiao M-T (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • You JS, Jones PA (2012) Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22:9–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao F, Zhang Z-W, Zhang J, Zhang S, Zhang H, Zhao C, Chen Y, Luo L, Tong W-M, Li C (2021) Loss of 5-hydroxymethylcytosine as an epigenetic signature that correlates with poor outcomes in patients with medulloblastoma. Front Oncol 11:603686

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Eskisehir Osmangazi University, Medical Faculty, Eskişehir, Turkey

    Sevilhan Artan

  2. Department of Neurosurgery, Eskisehir Osmangazi University, Medical Faculty, Eskişehir, Turkey

    Ali Arslantas

Authors
  1. Sevilhan Artan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Arslantas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sevilhan Artan .

Editor information

Editors and Affiliations

  1. Faculty of Medicine, Department of Medical Genetics, European University of Lefke, Lefke, Northern Cyprus, via Mersin, Türkiye

    Rasime Kalkan

Ethics declarations

A.A. and S.A. wrote the chapter. All authors read and approved the final manuscript.

The authors declare that they have no competing interests. Although some figures of the chapter are similar to the figures in the literature in the schematic description of the molecular mechanisms, all the figures in this section were produced and drawn by the authors themselves.

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Artan, S., Arslantas, A. (2023). The Epigenetics of Brain Tumors: Fundamental Aspects of Epigenetics in Glioma. In: Kalkan, R. (eds) Cancer Epigenetics. Epigenetics and Human Health, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-031-42365-9_7

Download citation

Publish with us

Policies and ethics

Search

Navigation