Journal of Neuro-Oncology

, Volume 70, Issue 2, pp 161–181

Molecular pathogenesis of oligodendroglial tumors

  • Judith W.M. Jeuken
  • Andreas Von Deimling
  • Pieter Wesseling


Based on their histopathological appearances, most diffusely infiltrative gliomas can be classified either as astrocytic tumors (As), pure oligodendroglial tumors (Os) or mixed oligoastrocytic tumors (OAs). The latter two may be grouped together as oligodendroglial tumors (OTs). The distinction between As and OTs is important because of the more favorable clinical behavior of OTs. Unfortunately, the histopathological delineation of OAs, Os and As can be difficult because of vague and subjective histopathological criteria. Over the last decade, the knowledge on the molecular genetic background of OTs has drastically increased. This review provides an overview of molecular genetic aberrations in OTs and discusses the pathobiological and clinical significance of these aberrations. In contrast to As, OTs frequently show frequent loss of heterozygosity on chromosome arms 1p and 19q. Since these aberrations are significantly correlated with clinically relevant parameters, such as prognosis and chemosensitivity, and given the difficulties in histopathological typing and grading of glial tumors, genetic testing should be included in routine glioma diagnostics. It is to be expected that the identification of the relevant tumor suppressor genes located on 1p and 19q will lead to more refined genetic tests for OTs. Furthermore, as microarray technology is rapidly increasing, it is likely that clinically relevant markers for OTs will be identified on other chromosomes and need to be included into routine glioma diagnostics as well.

loss of heterozygosity molecular genetics oligoastrocytoma oligodendroglioma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kleihues P, Cavenee WK: World Health Organization Classification of Tumours. Pathology and Genetics. Tumours of the Nervous System. International Agency for Research on Cancer (IARC) Press, Lyon, France, 1999Google Scholar
  2. 2.
    Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK: Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 79: 1381–1393, 1997Google Scholar
  3. 3.
    Giannini C, Scheithauer BW, Weaver AL, Burger PC, Kros JM, Mork S, Graeber MB, Bauserman S, Buckner JC, Burton J, Riepe R, Tazelaar HD, Nascimento AG, Crotty T, Keeney GL, Pernicone P, Altermatt H: Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading. J Neuropathol Exp Neurol 60: 248–262, 2001Google Scholar
  4. 4.
    Burger PC, Scheithauer BW: Tumors of the central nervous system, Armed Forces Institute of Pathology, Washington DC, 1994Google Scholar
  5. 5.
    von Deimling A, Louis DN, Wiestler OD: Molecular pathways in the formation of gliomas. Glia 15: 328–338, 1997Google Scholar
  6. 6.
    Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, Louis DN, Weistler OD, von Deimling A: Shared allelic losses on chromosome 1p and 19q suggest a common origin of oligodendrogliomas and oligoastrocytomas. J Neuropathol Exp Neurol 54: 91–95, 1995Google Scholar
  7. 7.
    Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP: Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 145: 1175–1190, 1994Google Scholar
  8. 8.
    Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein D, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN: Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90: 1473–1479, 1998Google Scholar
  9. 9.
    Burger PC: What is an oligodendroglioma? Brain Pathol 12: 257–259, 2002Google Scholar
  10. 10.
    DeAngelis LM: Brain tumors. N Eng J Med 344: 114–123, 2001Google Scholar
  11. 11.
    von Deimling A, Louis DN, von Ammon K, Petersen I, Wiestler OD, Seizinger BR: Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas. Cancer Res 52: 4277–4279, 1992Google Scholar
  12. 12.
    Bello MJ, Vaquero J, de Campos JM, Kusak ME, Sarasa JL, Saez-Castresana J, Pestana A, Rey JA: Molecular analysis of chromosome 1 abnormalities in human gliomas reveals frequent loss of 1p in oligodendroglial tumors. Int J Cancer 57: 172–175, 1994Google Scholar
  13. 13.
    Bello MJ, Leone PE, Vaquero J, de Campos JM, Kusak ME, Sarasa JL: Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors. Int J Cancer 64: 207–210, 1995Google Scholar
  14. 14.
    Maintz D, Fiedler K, Koopmann J, Rollbrocker B, Nechev S, Lenartz D, Stangl AP, Louis DN, Schramm J, Wiestler OD, von Deimling A: Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol Exp Neurol 56: 1098–1104, 1997Google Scholar
  15. 15.
    Rosenberg JE, Lisle DK, Burwick A, Ueki K, von Deimling A, Mohrenweiser HW, Louis DN: Refined deletion mapping of 19q glioma tumor suppressor gene to the D19S412-STD interval. Oncogene 13: 2483–2485, 1996Google Scholar
  16. 16.
    Ritland SR, Ganju V, Jenkins RB: Region-specific loss of heterozygosity on chromosome 19 is related to the morphologic type of human glioma. Gen Chrom Cancer 12: 277–282, 1995Google Scholar
  17. 17.
    von Deimling A, Nagel J, Bender B, Lenartz D, Schramm J, Louis DN, Weistler OD: Deletion mapping of chromosome 19 in human gliomas. Int J Cancer 57: 676–680, 1994Google Scholar
  18. 18.
    Iuchi T, Namba H, Iwadate Y, Shishikura T, Kageyama H, Nakamura Y, Ohira M, Yamaura A, Osato K, Sakiyama S, Nakagawara A: Identification of the small interstitial deletion at chromosome band 1p34-p35 and its association with poor outcome in oligodendroglial tumors. Genes Chromosomes Cancer 35: 170–175, 2002Google Scholar
  19. 19.
    Ransom DT, Ritland SR, Moertel CA, Dahl RJ, O'Fallon JR, Scheithauer BW, Kimmel DW, Kelly PJ, Olopade OI, Diaz MO, Jenkins RB: Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo-astrocytomas. Gen Chromosomes Cancer 5: 357–374, 1992Google Scholar
  20. 20.
    Jeuken JWM, Sprenger SHE, Wesseling P: Comparative genomic hybridization: Practical guidelines. Diagn Mol Pathol 11: 193–203, 2002Google Scholar
  21. 21.
    Jeuken JWM, Sprenger SHE, Wesseling P, Macville MVE, von Deimling A, Teepen HLJM, van Overbeeke JJ, Boerman RH: Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization. J Neuropathol Exp Neurol 58: 606–612, 1999Google Scholar
  22. 22.
    Jeuken JWM, Sprenger SHE, Boerman RH, von Deimling A, Teepen HLJM, van Overbeeke JJ, Wesseling P: Subtyping of oligo-astrocytic tumours by comparative genomic hybridisation. J Pathol 194: 81–87, 2001Google Scholar
  23. 23.
    Jeuken JWM, Sprenger SHE, Vermeer H, Kappelle AC, Boerman RH, Wesseling P: Chromosomal imbalances in primary oligodendroglial tumors and their recurrences; clues for malignant progression as detected by CGH. J Neurosurg 96: 559–564, 2002Google Scholar
  24. 24.
    Kros JM, van Run PRWA, Alers JC, Beverloo B, van den Bent M, Avezaat CJJ, van Dekken H: Genetic aberrations in oligodendroglial tumours: an analysis using comparative genomic hybridization (CGH). J Pathol 188: 282–288, 1999Google Scholar
  25. 25.
    Bigner SH, Matthews MR, Rasheed BKA, Wiltshire RN, Friedman HS, Friedman AH, Stenzel TT, Dawes DM, McLendon RE, Bigner DD: Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization. Am J Pathol 155: 375–386, 1999Google Scholar
  26. 26.
    Jeuken JWM, Boots-Sprenger SHE, Wesseling P: Chromosomal imbalances in oligodendroglial tumors as detected by comparative genomic hybridization (CGH). In: Zhang W, Fuller GN (eds) Genomic and Molecular Neuro-Onclogy. Jones and Bartlett Publishers, Sudbury MA, 2004, pp 185–198Google Scholar
  27. 27.
    Smith JS, Perry A, Borell TJ, Lee HK, Fallen JO, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB: Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18: 636–645, 2000Google Scholar
  28. 28.
    van den Bent MJ, Looijenga LHJ, Langberg K, Dinjens W, Gravenland W, Uytdewilligen L, Sillevis Smitt PA, Jenkins RB, Kros JM: Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features. Cancer 97: 1276–1284, 2003Google Scholar
  29. 29.
    Dong ZQ, Pang JC, Tong CY, Zhou LF, Ng HK: Clonality of oligoastrocytomas. Hum Pathol 33: 528–535, 2002Google Scholar
  30. 30.
    Tenebaum L, Teugels E, Dogusan Z, Avellana-Adalid V, Hooghe-Peters EL: Plastic phenotype of human oligodendroglial tumour cells in vitro. Neuropathol Applied Neurobiol 22: 302–310, 1996Google Scholar
  31. 31.
    Raff MC, Miller R, Noble M: A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303: 390–396, 1983Google Scholar
  32. 32.
    Kraus JA, Lamszus K, Glesmann N, Beck M, Wolter M, Sabel M, Krex D, Klockgether T, Reifenberger G, Schlegel U: Molecular genetic alterations in glioblastomas with oligodendroglial component. Acta Neuropathol (Berl) 101: 311–320, 2001Google Scholar
  33. 33.
    He J, Mokhtari K, Sanson M, Marie Y, Kujas M, Huguet S, Leuraud P, Capelle L, Delattre JY, Poirier J, Hoang-Xuan K: Glioblastomas with an oligodendroglial component: a pathological and molecular study. J Neuropathol Exp Neurol 60: 863–871, 2001Google Scholar
  34. 34.
    Bigner SH, Rasheed A, Wiltshire RN, McLendon RE: Morphologic and molecular genetic aspects of oligodendroglial neoplasms. Neuro-Oncology 1: 52–60, 1999Google Scholar
  35. 35.
    Raghavan R, Balani J, Perry A, Margraf L, Vono MB, Cai DX, Wyatt RE, Rushing EJ, Bowers DC, Hynan LS, White CL, III: Pediatric oligodendrogliomas: a study of molecular alterations on 1p and 19q using fluorescence in situ hybridization. J Neuropathol Exp Neurol 62: 530–537, 2003Google Scholar
  36. 36.
    Prayson RA, Castilla EA, Hartke M, Pettay J, Tubbs RR, Barnett GH: Chromosome 1p allelic loss by fluorescence in situ hybridization is not observed in dysembryoplastic neuroepithelial tumors. Am J Clin Pathol 118: 512–517, 2002Google Scholar
  37. 37.
    Perry A, Fuller CE, Banerjee R, Brat DJ, Scheithauer BW: Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics. Front Biosci 8: a1–a9, 2003Google Scholar
  38. 38.
    Tong CY, Ng HK, Pang JC, Hu J, Hui AB, Poon WS: Central neurocytomas are genetically distinct from oligodendrogliomas and neuroblastomas. Histopathology 37: 160–165, 2000Google Scholar
  39. 39.
    Perry A, Scheithauer BW, Macaulay RJ, Raffel C, Roth KA, Kros JM: Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol 61: 947–955, 2002Google Scholar
  40. 40.
    Knudson AG Jr: Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68: 820–823, 1971Google Scholar
  41. 41.
    Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D: Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90: 809–819, 1997Google Scholar
  42. 42.
    Alonso ME, Bello MJ, Gonzalez-Gomez P, Lomas J, Arjona D, de Campos JM, Kusak ME, Sarasa JL, Isla A, Rey JA: Mutation analysis of the p73 gene in nonastrocytic brain tumours. Br J Cancer 85: 204–208, 2001Google Scholar
  43. 43.
    Mai M, Huang H, Reed C, Qian C, Smith JS, Alderete B, Jenkins R, Smith DI, Liu W: Genomic organization and mutation analysis of p73 in oligodendrogliomas with chromosome 1p-arm deletions. Genomics 51: 359–363, 1998Google Scholar
  44. 44.
    Dong S, Pang JC, Hu J, Zhou LF, Ng HK: Transcriptional inactivation of TP73 expression in oligodendroglial tumors. Int J Cancer 98: 370–375, 2002Google Scholar
  45. 45.
    Watanabe T, Huang H, Nakamura M, Wischhusen J, Weller M, Kleihues P, Ohgaki H: Methylation of the p73 gene in gliomas. Acta Neuropathol (Berl) 104: 357–362, 2002Google Scholar
  46. 46.
    Mai M, Qian C, Yokomizo A, Tindall DJ, Bostwick D, Polychronakos C, Smith DI, Liu W: Loss of imprinting and allele switching of p73 in renal cell carcinoma. Oncogene 17: 1739–1741, 1998Google Scholar
  47. 47.
    Mai M, Yokomizo A, Qian C, Yang P, Tindall DJ, Smith DI, Liu W: Activation of p73 silent allele in lung cancer. Cancer Res 58: 2347–2349, 1998Google Scholar
  48. 48.
    Melino G, De LV, Vousden KH: p73: Friend or foe in tumorigenesis. Nat Rev Cancer 2: 605–615, 2002Google Scholar
  49. 49.
    Husemann K, Wolter M, Buschges R, McLendon RE: Identification of two distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C gene from 1p32 in oligodendroglial tumors. J Neuropathol Exp Neurol 58: 1041–1050, 1999Google Scholar
  50. 50.
    Pohl U, Cairncross JG, Louis DN: Homozygous deletions of the CDKN2C/p18INK4C gene on the short arm of chromosome 1 in anaplastic oligodendrogliomas. Brain Pathol 9: 639–643, 1999Google Scholar
  51. 51.
    He J, Hoang-Xuan K, Marie Y, Leuraud P, Mokhtari K, Kujas M, Delattre JY, Sanson M: P1 8 tumor suppressor gene and progression of oligodendrogliomas to anaplasia. Neurology 55: 867–869, 2000Google Scholar
  52. 52.
    Bello MJ, de Campos JM, Vaquero J, Ruiz-Barnes P, Kusak ME, Sarasa JL, Rey JA: hRAD54 gene and 1p high-resolution deletion-mapping analyses in oligodendrogliomas. Cancer Genet Cytogenet 116: 142–147, 2000Google Scholar
  53. 53.
    Ritland SR, Ganju V, Jenkins RB: Region-specific loss of heterozygosity on chromosome 19 is related to the morphologic type of human glioma. Gen Chrom Cancer 12: 277–282, 1995Google Scholar
  54. 54.
    Schmid JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB: Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18: 636–645, 2000Google Scholar
  55. 55.
    Ransom DT, Ritland SR, Kimmel DW, Moertel CA, Dahl RJ, Scheithauer BW, Kelly PJ, Jenkins RB: Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas. Genes, Chrom Cancer 5: 348–356, 1992Google Scholar
  56. 56.
    Rubio MP, Correa KM, Ueki K, Mohrenweiser HW, Gusella JF, von Deimling A, Louis DN: The putative glioma tumor suppressor gene on chromosome 19q maps between APOC2 and HRC. Cancer Res 54: 4760–4763, 1994Google Scholar
  57. 57.
    Ashworth LK, Batzer MA, Brandriff B, Branscomb E, De Jong P, Garcia E, Garnes JA, Gordon LA, Lamerdin JE, Lennon G, Mohrenweiser H, Olsen AS, Slezak T, Carrano AV: An integrated metric physical map of human chromosome 19. Nature genet 11: 422–427, 1995Google Scholar
  58. 58.
    Smith JS, Tachibana I, Lee HK, Qian J, Pohl U, Mohrenweiser HW, Borell TJ, Hosek SM, Soderberg CL, von Deimling A, Perry A, Scheithauer BW, Louis DN, Jenkins RB: Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using fluorescence in situ hybridization and novel microsatellite markers. Genes Chromosomes Cancer 29: 16–25, 2000Google Scholar
  59. 59.
    Smith JS, Tachibana I, Pohl U, Lee HK, Thanarajasingam U, Portier BP, Ueki K, Ramaswamy S, Billings SJ, Mohrenweiser HW, Louis DN, Jenkins RB: A transcript map of the chromosome 19 q-arm glioma tumor suppressor region. Genomics 64: 44–50, 2000Google Scholar
  60. 60.
    Pohl U, Smith JS, Tachibana I, Ueki K, Lee HK, Ramaswamy S, Wu Q, Mohrenweiser HW, Jenkins RB, Louis DN: EHD2, EHD3, and EHD4 encode novel members of a highly conserved family of EH domaincontaining proteins. Genomics 63: 255–262, 2000Google Scholar
  61. 61.
    Largaespada DA: Haploinsufficiency for tumor suppression: the hazards of being single and living a long time. J Exp Med 193: F15–F18, 2001Google Scholar
  62. 62.
    Jirtle RL: Genomic imprinting and cancer. Exp Cell Res 248: 18–24, 1999Google Scholar
  63. 63.
    Kohda T, Asai A, Kuroiwa Y, Kobayashi S, Aisaka K, Nagashima G, Yoshida MC, Kondo Y, Kagiyama N, Kirino T, Kaneko-Ishino T, Ishino F: Tumour suppressor activity of human imprinted gene PEG3 in a glioma cell line. Genes Cells 6: 237–247, 2001Google Scholar
  64. 64.
    Maegawa S, Yoshioka H, Itaba N, Kubota N, Nishihara S, Shirayoshi Y, Nanba E, Oshimura M: Epigenetic silencing of PEG3 gene expression in human glioma cell lines. Mol Carcinog 31: 1–9, 2001Google Scholar
  65. 65.
    Sanson M, Leuraud P, Marie Y, Delattre JY, Hoang-Xuan K: Preferential loss of paternal 19q, but not 1p, alleles in oligodendrogliomas. Ann Neurol 52: 105–107, 2002Google Scholar
  66. 66.
    Hartmann C, Mueller W, Lass U, Stockhammer F, von Eckardstein K, Veelken J, Jeuken J, Wick W, von Deimling A: No preferential loss of paternal 19q alleles in oligodendroglial tumors. Ann Neurol 54: 256–258, 2003Google Scholar
  67. 67.
    Herman JG, Baylin SB: Gene silencing in cancer in association with promotor hypermethylation. New England J Med 349: 2042–2054, 2003Google Scholar
  68. 68.
    von Deimling A, Fimmers R, Schmidt MC, Bender B, Fassbender F, Nagel J, Jahnke R, Kaskel P, Duerr E, Koopmann J, Maintz D, Steinbeck S, Wick W, Platten M, Muller DJ, Przkora R, Waha A, Blumcke B, Wellenreuther R, Meyer-Puttlitz B, Schmidt O, Mollenhauer J, Poustka A, Stangl AP, Lenartz D, von Ammon K, Henson JW, Schramm J, Louis DN, Wiestler OD: Comprehensive allelotype and genetic analysis of 466 human nervous system tumors. J Neuropathol and Exp Neurol 56: 544–558, 2000Google Scholar
  69. 69.
    Zhu J, Santarius T, Wu X, Tsong J, Guha A, Wu JK, Hudson TJ, Black PM: Screening for loss of heterozygosity and microsatellite instability in oligodendrogliomas. Genes, Chrom Cancer 21: 207–216, 1998Google Scholar
  70. 70.
    Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N, Fujimaki T, Hojo S, Kubo O, Ide T, Usui M, Ochiai C, Ito S, Takahashi H, Mukasa A, Asai A, Kirino T: Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors. Clin Cancer Res 8: 196–201, 2002Google Scholar
  71. 71.
    Burger PC, Minn AY, Smith JS, Borell TJ, Jedlicka AE, Huntley BK, Goldthwaite BT, Jenkins RB, Feuerstein BG: Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma. A study on paraffin-embedded sections. Mod Pathol 14: 842–853, 2001Google Scholar
  72. 72.
    Wolter M, Reifenberger J, Blaschke B, Ichimura K, Schmidt EE, Collins VP, Reifenberger G: Oligodendroglial tumors frequently demonstrate hypermethylation of the CDKN2A (MTS1, p16INK4a), p14ARF, and CDKN2B (MTS2, p15INK4b) tumor suppressor genes. J Neuropathol Exp Neurol 60: 1170–1180, 2001Google Scholar
  73. 73.
    Watanabe T, Nakamura M, Kros JM, Burkhard C, Yonekawa Y, Kleihues P, Ohgaki H: Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Acta Neuropathol (Berl) 103: 267–275, 2002Google Scholar
  74. 74.
    Hoang-Xuan K, Aguirre-Cruz L, Mokhtari K, Marie Y, Sanson M: OLIG-1 and 2 gene expression and oligodendroglial tumours. Neuropathol Appl Neurobiol 28: 89–94, 2002Google Scholar
  75. 75.
    Ino Y, Betensky RA, Zlatescu MC, Sasaki H, Macdonald DR, Stemmer-Rachamimov AO, Ramsay DA, Cairncross JG, Louis DN: Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 7: 839–845, 2001Google Scholar
  76. 76.
    Watanabe T, Yokoo H, Yokoo M, Yonekawa Y, Kleihues P, Ohgaki H: Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas. J Neuropathol Exp Neurol 60: 1181–1189, 2001Google Scholar
  77. 77.
    Mohapatra G, Bollen AW, Kim DH, Lamborn K, Moore DH, Prados MD, Feuerstein BG: Genetic analysis of glioblastoma multiforme provides evidence for subgroups within the grade. Gen Chromosomes Cancer 21: 195–206, 1998Google Scholar
  78. 78.
    Huhn SL, Mohapatra G, Bollen A, Lamborn K, Prados MD, Feuerstein BG: Chromosomal imbalances in glioblastoma multiforme by comparative genomic hybridization: correlation with radiation treatment. Clin Cancer Res 5: 1435–1443, 1999Google Scholar
  79. 79.
    Weber RG, Sabel M, Reifenberger J, Sommer C, Oberstrass J, Reifenberger G, Kiessling M, Cremer T: Characterization of genomic alterations associated with glioma progression by comparative genomic hybridization. Oncogene 13: 983–994, 1996Google Scholar
  80. 80.
    Schrock E, Blume C, Meffert M, du Manoir S, Bersch W, Kiessling M, Lozanowa T, Thiel G, Witkowski R, Ried T, Cremer T: Recurrent gain of chromosome arm 7q in lowgrade astrocytic tumors studied by comparative genomic hybridization. Gen Chrom Cancer 15: 199–205, 1996Google Scholar
  81. 81.
    Nishizaki T, Kubota H, Harada K, Ito H, Suzuki M, Sasaki K: Clinical evidence of distinct subgroups of astrocytic tumors defined by comparative genomic hybridization. Hum Pathol 31: 608–614, 2000Google Scholar
  82. 82.
    von Deimling A: Neoplasia. Molecular genetic classification of astrocytic and oligodendroglial tumors. Brain Pathol 7: 1311–1313, 1997Google Scholar
  83. 83.
    Hoang-Xuan K, He J, Huguet S, Mokhtari K, Marie Y, Kujas M, Leuraud P, Capelle L, Delattre JY, Poirier J, Broet P, Sanson M: Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression. Neurology 57: 1278–1281, 2001Google Scholar
  84. 84.
    Schmidt EE, Ichimura K, Reifenberger G, Collins P: CDKN2(p 16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. Cancer Res 54: 6321–6324, 1994Google Scholar
  85. 85.
    He J, Alien R, Collins P, Allalunis-Turner J, Godbout R, Day RS, James CD: CDK4 amplification is an alternative mechanism to p16 gene homozygeous deletion in glioma cell lines. Cancer Res 54: 5804–5807, 1994Google Scholar
  86. 86.
    He J, Olson J, James D: Lack of p161KN4 or retinablastoma protein (pRB), or amplification-associated over-expression of cdk4 is observed in distinct subsets of malignant glial tumors and cell lines. Cancer Res 55: 4833–4836, 1995Google Scholar
  87. 87.
    Ueki K, Ono Y, Henson JW, Efird JT, von Deimling A, Louis DN: CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res 56: 150–153, 1996Google Scholar
  88. 88.
    Biernat W, Kleihues P, Yonekawa Y, Ohgaki H: Amplification and over-expression of mdm2 in primary (de novo) glioblastomas. J Neuropathol Exp Neurol 56: 180–185, 1997Google Scholar
  89. 89.
    Hui AB, Lo K, Yin X, Poon W, Ng H: Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization. Lab Invest 81: 717–723, 2001Google Scholar
  90. 90.
    Shai R, Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF, Mischel PS, Nelson SF: Gene expression profiling identifies molecular subtypes of gliomas. Oncogene 22: 4918–4923, 2003Google Scholar
  91. 91.
    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: Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63: 1602–1607, 2003Google Scholar
  92. 92.
    van den Boom J., Wolter M, Kuick R, Misek DE, Youkilis AS, Wechsler DS, Sommer C, Reifenberger G, Hanash SM: Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. Am J Pathol 163: 1033–1043, 2003Google Scholar
  93. 93.
    Watson MA, Perry A, Budhjara V, Hicks C, Shannon WD, Rich KM: Gene expression profiling with oligonucleotide microarrays distinguishes world health orginization grade of oligodendrogliomas. Cancer Res 61: 1825–1829, 2001Google Scholar
  94. 94.
    Mukasa A, Ueki K, Matsumoto K, Tsutsumi S, Nishikawa R, Fujimaki T, Asia A, Kirino T, Aburatani H: Distinction in gene expression profiles of oligodendrogliomas with and without allelic loss of 1p. Oncogene 21: 3961–3968, 2002Google Scholar
  95. 95.
    Bauman GS, Ino Y, Ueki K, Zlatescu MC, Fisher BJ, Macdonald DR, Stitt L, Louis DN, Cairncross JG: Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas. Int J Radiation Oncology Biol Phy 48: 825–830, 2000Google Scholar
  96. 96.
    Bissola L, Eoli M, Polio B, Merciai BM, Silvani A, Salsano E, Maccagnano C, Bruzzone MG, Fuhrman Conti AM, Solero CL, Giombini S, Broggi G, Boiardi A, Finocchiaro G: Association of chromosome 10 losses and negative prognosis in oligoastrocytomas. Ann Neurol 52: 842–845, 2002Google Scholar
  97. 97.
    Hashimoto N, Murakami M, Takahashi Y, Fujimoto M, Inazawa J, Mineura K: Correlation between genetic alteration and long-term clinical outcome of patients with oligodendroglial tumors, with identification of a consistent region of deletion on chromosome arm 1p. Cancer 97: 2254–2261, 2003Google Scholar
  98. 98.
    Ino Y, Zlatescu MC, Sasaki H, Macdonald DR, Stemmer-Rachamimov AO, Jhung S, Ramsay DA, von Deimling A, Louis DN, Cairncross JG: Long survival and therapeutic responses in patients with histologically disparate highgrade gliomas demonstrating chromosome 1p loss. J Neurosurg 92: 983–990, 2000Google Scholar
  99. 99.
    Schmidt MC, Antweiler S, Urban N, Mueller W, Kuklik A, Meyer-Puttlitz B, Weistler OD, Louis DN, Fimmers R, von Deimling A: Impact of genotype and morphology on the prognosis of glioblastoma. J Neuropathol Exp Neurol 61: 321–328, 2002Google Scholar
  100. 100.
    Arslantas A, Artan S, Oner U, Muslumanoglu H, Durmaz R, Cosan E, Atasoy MA, Basaran N, Tel E: The importance of genomic copy number changes in the prognosis of glioblastoma multiforme. Neurosurg Rev 2003Google Scholar
  101. 101.
    van den Bent MJ, Chinot OL, Cairncross JG: Recent developments in the molecular characterization and treatment of oligodendroglial tumors. Neurooncol 5: 128–138, 2003Google Scholar
  102. 102.
    van den Bent MJ, Chinot O, Boogerd W, Bravo MJ, Taphoorn MJ, Kros JM, Van Der Rijt CC, Vecht CJ, De Beule N, Baron B: Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. Ann Oncol 14: 599–602, 2003Google Scholar
  103. 103.
    Chinot O: Chemotherapy for the treatment of oligodendroglial rumors. Semin Oncol 28: 13–18, 2001Google Scholar
  104. 104.
    Chinot OL, Honore S, Dufour H, Barrie M, Figarella-Branger D, Muracciole X, Braguer D, Martin PM, Grisoli F: Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy. J Clin Oncol 19: 2449–2455, 2001Google Scholar
  105. 105.
    Chahlavi A, Kanner A, Peereboom D, Staugaitis SM, Elson P, Barnett G: Impact of chromosome 1p status in response of oligodendroglioma to temozolomide: preliminary results. J Neurooncol 61: 267–273, 2003Google Scholar
  106. 106.
    Macdonald DR: Temozolomide for recurrent high-grade glioma. Semin Oncol 28: 3–12, 2001Google Scholar
  107. 107.
    Betensky RA, Louis DN, Cairncross JG: Influence of unrecognized molecular heterogeneity on randomized clinical trials. J Clin Oncol 20: 2495–2499, 2002Google Scholar
  108. 108.
    Lu QR, Park JK, Noll E, Chan JA, Alberta J, Yuk D, Alzamora MG, Louis DN, Stiles CD, Rowitch DH, Black PM: Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. Proc Natl Acad Sci USA 98: 10851–10856, 2001Google Scholar
  109. 109.
    Marie Y, Sanson M, Mokhtari K, Leuraud P, Kujas M, Delattre JY, Poirier J, Zalc B, Hoang-Xuan K: OLIG2 as a specific marker of oligodendroglial tumour cells. Lancet 358: 298–300, 2001Google Scholar
  110. 110.
    Ohnishi A, Sawa H, Tsuda M, Sawamura Y, Itoh T, Iwasaki Y, Nagashima K: Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in different types of human gliomas. J Neuropathol Exp Neurol 62: 1052–1059, 2003Google Scholar
  111. 111.
    Blumcke I, Becker AJ, Normann S, Hans V, Riederer BM, Krajewski S, Wiestler OD, Reifenberger G: Distinct expression pattern of microtubule-associated protein-2 in human oligodendrogliomas and glial precursor cells. J Neuropathol Exp Neurol 60: 984–993, 2001Google Scholar
  112. 112.
    Suzuki SO, Kitai R, Llena J, Lee SC, Goldman JE, Shafit-Zagardo B: MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration. J Neuropathol Exp Neurol 61: 403–412, 2002Google Scholar
  113. 113.
    Kros JM, Pieterman H, van Eden CG, Avezaat CJ: Oligodendroglioma: the Rotterdam-Dijkzigt experience. Neurosurgery 34: 959–966, 1994Google Scholar
  114. 114.
    Zlatescu MC, TehraniYazdi A, Sasaki H, Megyesi JF, Betensky RA, Louis DN, Cairncross JG: Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms. CancerRes 61: 6713–6715, 2001Google Scholar
  115. 115.
    Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J, Veelken J, Schramm J, Weller M, Wiestler OD, Louis DN, von Deimling A: Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. Am J Pathol 161: 313–319, 2002Google Scholar
  116. 116.
    Spassky N, Olivier C, Perez-Villegas E, Goujet-Zalc C, Martinez S, Thomas J, Zalc B: Single or multiple oligodendroglial lineages: a controversy. Glia 29: 143–148, 2000Google Scholar
  117. 117.
    Dai C, Celestino JC, Okada Y, Louis DN, Fuller GN, Holland EC: PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 15: 1913–1925, 2001Google Scholar
  118. 118.
    Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN: Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet 25: 55–57, 2000Google Scholar
  119. 119.
    Holland EC, Li Y, Celestino J, Dai C, Schaefer L, Sawaya RA, Fuller GN: Astrocytes give rise to oligodendrogliomas and astrocytomas after gene transfer of polyoma virus middle T antigen in vivo. Am J Pathol 157: 1031–1037, 2000Google Scholar
  120. 120.
    Hatanpaa KJ, Burger PC, Eshleman JR, Murphy KM, Berg KD: Molecular diagnosis of oligodendroglioma in paraffin sections. Lab Invest 83: 419–428, 2003Google Scholar
  121. 121.
    Smith JS, Alderete BE, Minn Y, Borell T, Perry A, Mohapatra G, Smith SM, Kimmel D, Fallon JO, Tales A, Feuerstein BG, Burger PC, Scheithauer BW: Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18: 4144–4152, 1999Google Scholar
  122. 122.
    Gelpi E, Ambros IM, Birner P, Luegmayr A, Drlicek M, Fischer I, Kleinert R, Maier H, Huemer M, Gatterbauer B, Anton J, Rossler K, Budka H, Ambros PF, Hainfellner JA: Fluorescent in situ hybridization on isolated tumor cell nuclei: a sensitive method for 1p and 19q deletion analysis in paraffin-embedded oligodendroglial tumor specimens. Mod Pathol 16: 708–715, 2003Google Scholar
  123. 123.
    Reifenberger G, Louis DN: Oligodendroglioma: Toward molecular definitions in diagnostic neurooncology. J Neuropathol Exp Neurol 62: 111–126, 2003Google Scholar
  124. 124.
    Nigro JM, Takahashi MA, Ginzinger DG, Law M, Passe S, Jenkins RB, Aldape KD: Detection of 1p and 19q loss in oligodendroglioma by quantative microsatellite analysis, a real-time quantative polymerase chain reaction assay. Am J Pathol 158: 1253–1262, 2001Google Scholar
  125. 125.
    Gizinger DG, Godfrey TE, Nigro JM, Moore DH, Suzuki SO, Pallavicini MG, Gray JW, Jensen RH: Measurement of DNA copy number at microsatellite loci using quantitative PCR analysis. Cancer Res 60: 5405–5409, 2000Google Scholar
  126. 126.
    Yong WH, Chou D, Ueki K, Harsh GR, von Deimling A, Gusella JF, Mohrenweiser HW, Louis DN: Chromosome 19q deletions in human gliomas overlap telomeric to D19S219 and may target a 425 kb region centromeric to D19S112. J Neuropathol Exp Neurol 54: 622–626, 1995Google Scholar
  127. 127.
    Nakamura M, Yang F, Fujisawa H, Yonekawa Y, Kleihues P, Ohgaki H: Loss of heterozygosity on chromosome 19 in secondary glioblastomas. J Neuropathol Exp Neurol 59: 539–543, 2000Google Scholar
  128. 128.
    Hartmann C, Johnk L, Kitange G, Wy Y, Ashworth LK, Jenkins RB, Louis DN: Transcript map of the 3.7-Mb D19S112-D19S246 candidate tumor suppressor region on the long arm of chromosome 19. Cancer Res 62: 4100–4108, 2002Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Judith W.M. Jeuken
    • 1
  • Andreas Von Deimling
    • 2
  • Pieter Wesseling
    • 1
  1. 1.Department of PathologyUniversity Medical Centre NijmegenNijmegenThe Netherlands
  2. 2.Department of NeuropathologyCharitéGermany

Personalised recommendations