Skip to main content

Molecular Classification of Gliomas

  • Chapter
  • First Online:
Tumors of the Central Nervous System, Volume 1

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 1))

  • 1916 Accesses

Abstract

Molecular markers have been intensively explored to overcome the limitations in the histopathological diagnosis of gliomas. Gene expression profiling, i.e., genome wide analysis of gene expression, has given rise to new molecular classification schemes. In particular, diagnostic systems for differential diagnosis of anaplastic oligodendroglioma and glioblastoma, or for prediction of prognosis for displastic astrocytoma, anaplastic astrocytoma, anaplastic oligodendroglioma and glioblastoma have been constructed through studies employing machine learning. Classification by gene expression profiling has also revealed molecular classes with distinct biological characteristics not detected by histopathology. The promoter methylation of the O6-methylguanine methyltransferase gene has been reported as prognostic as well as predictive for alkylating agents such as temozolomide in glioblastoma. Partly due to technical difficulties in detection of methylation with PCR, the results of studies are not necessarily consistent. However, a recent study with bisulfite sequencing revealed good prognostic ability, which promises future clinical application. Among other molecular markers, 1p-/19q- has been established as a prognostic factor in oligodendroglial tumors, and is being used as a diagnostic test in several institutes. IDH1 and EGFR are being explored for differentiation of primary and secondary glioblastoma, and as a possible predictive factor for molecular targeted drugs, respectively. Adequate prospective studies will help evaluate the ability of the above classification schemes as diagnostics tests to support histopathological diagnoses.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

References

  • Brandes AA, Franceschi E, Tosoni A, Hegi ME, Stupp R (2008) Epidermal growth factor receptor inhibitors in neuro-oncology: hopes and disappointments. Clin Cancer Res 14(4):957–960

    Article  PubMed  CAS  Google Scholar 

  • Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W (2006) Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: intergroup radiation therapy oncology group trial 9402. J Clin Oncol 24(18):2707–2714

    Article  PubMed  CAS  Google Scholar 

  • Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90(19):1473–1479

    Article  PubMed  CAS  Google Scholar 

  • Colella S, Shen L, Baggerly KA, Issa JP, Krahe R (2003) Sensitive and quantitative universal pyrosequencing methylation analysis of CpG sites. Biotechniques 35(1):146–150

    PubMed  CAS  Google Scholar 

  • Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK (1997) Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 79(7):1381–1393

    Article  PubMed  CAS  Google Scholar 

  • Dunn J, Baborie A, Alam F, Joyce K, Moxham M, Sibson R, Crooks D, Husband D, Shenoy A, Brodbelt A, Wong H, Liloglou T, Haylock B, Walker C (2009) Extent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapy. Br J Cancer 101(1):124–131

    Article  PubMed  CAS  Google Scholar 

  • Dupuy A, Simon RM (2007) Critical review of published microarray studies for cancer outcome and guidelines on statistical analysis and reporting. J Natl Cancer Inst 99(2):147–157

    Article  PubMed  Google Scholar 

  • Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95(25):14863–14868

    Article  PubMed  CAS  Google Scholar 

  • Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343(19):1350–1354

    Article  PubMed  CAS  Google Scholar 

  • Freije WA, Castro-Vargas FE, Fang Z, Horvath S, Cloughesy T, Liau LM, Mischel PS, Nelson SF (2004) Gene expression profiling of gliomas strongly predicts survival. Cancer Res 64(18):6503–6510

    Article  PubMed  CAS  Google Scholar 

  • Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27(28):4733–4740

    Article  PubMed  CAS  Google Scholar 

  • Godard S, Getz G, Delorenzi M, Farmer P, Kobayashi H, Desbaillets I, Nozaki M, Diserens AC, Hamou MF, Dietrich PY, Regli L, Janzer RC, Bucher P, Stupp R, de Tribolet N, Domany E, Hegi ME (2003) Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Res 63(20):6613–6625

    PubMed  CAS  Google Scholar 

  • Gravendeel LA, Kouwenhoven MC, Gevaert O, de Rooi JJ, Stubbs AP, Duijm JE, Daemen A, Bleeker FE, Bralten LB, Kloosterhof NK, De Moor B, Eilers PH, van der Spek PJ, Kros JM, Sillevis Smitt PA, van den Bent MJ, French PJ (2009) Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer Res 69(23):9065–9072

    Article  PubMed  CAS  Google Scholar 

  • Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003

    Article  PubMed  CAS  Google Scholar 

  • Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109

    Article  PubMed  Google Scholar 

  • Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139

    Article  PubMed  CAS  Google Scholar 

  • Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J, Felsberg J, Kahl P, Buttner R, Pietsch T, Waha A (2007) Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn 9(3):368–381

    Article  PubMed  CAS  Google Scholar 

  • Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63(7):1602–1607

    PubMed  CAS  Google Scholar 

  • Park CK, Park SH, Lee SH, Kim CY, Kim DW, Paek SH, Kim DG, Heo DS, Kim IH, Jung HW (2009) Methylation status of the MGMT gene promoter fails to predict the clinical outcome of glioblastoma patients treated with ACNU plus cisplatin. Neuropathology 29(4):443–449

    Article  PubMed  Google Scholar 

  • Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr., Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321(5897):1807–1812

    Article  PubMed  CAS  Google Scholar 

  • Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, Misra A, Nigro JM, Colman H, Soroceanu L, Williams PM, Modrusan Z, Feuerstein BG, Aldape K (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9(3):157–173

    Article  PubMed  CAS  Google Scholar 

  • Preusser M, Charles Janzer R, Felsberg J, Reifenberger G, Hamou MF, Diserens AC, Stupp R, Gorlia T, Marosi C, Heinzl H, Hainfellner JA, Hegi M (2008) Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker. Brain Pathol 18(4):520–532

    PubMed  CAS  Google Scholar 

  • Shai R, Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF, Mischel PS, Nelson SF (2003) Gene expression profiling identifies molecular subtypes of gliomas. Oncogene 22(31):4918–4923

    Article  PubMed  CAS  Google Scholar 

  • Shirahata M, Iwao-Koizumi K, Saito S, Ueno N, Oda M, Hashimoto N, Takahashi JA, Kato K (2007) Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis. Clin Cancer Res 13(24):7341–7356

    Article  PubMed  CAS  Google Scholar 

  • Shirahata M, Oba S, Iwao-Koizumi K, Saito S, Ueno N, Oda M, Hashimoto N, Ishii S, Takahashi JA, Kato K (2009) Using gene expression profiling to identify a prognostic molecular spectrum in gliomas. Cancer Sci 100(1):165–172

    Article  PubMed  CAS  Google Scholar 

  • Smith JS, Perry A, Borell TJ, Lee HK, O’Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18(3):636–645

    PubMed  CAS  Google Scholar 

  • Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996

    Article  PubMed  CAS  Google Scholar 

  • van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, Malmstrom PO, Collette L, Pierart M, Mirimanoff R, Karim AB (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366(9490):985–990

    Article  PubMed  Google Scholar 

  • van‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536

    Article  Google Scholar 

  • Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, Moreau F, Hamou MF, Renard I, Delorenzi M, Flamion B, DiGuiseppi J, Bierau K, Hegi ME (2008) Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn 10(4):332–337

    Article  PubMed  CAS  Google Scholar 

  • Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174(4):1149–1153

    Article  PubMed  CAS  Google Scholar 

  • Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27(35):5874–5880

    Article  PubMed  CAS  Google Scholar 

  • Wong AJ, Ruppert JM, Bigner SH, Grzeschik CH, Humphrey PA, Bigner DS, Vogelstein B (1992) Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci USA 89(7):2965–2969

    Article  PubMed  CAS  Google Scholar 

  • Xiong Z, Laird PW (1997) COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res 25(12):2532–2534

    Article  PubMed  CAS  Google Scholar 

  • Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–773

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The author thanks Dr Mitsuaki Shirahata for critical reading of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kikuya Kato .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Kato, K. (2011). Molecular Classification of Gliomas. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 1. Tumors of the Central Nervous System, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0344-5_2

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-0344-5_2

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-0343-8

  • Online ISBN: 978-94-007-0344-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics