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Molecular Abnormalities in Gliomas

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Imaging of Brain Tumors with Histological Correlations

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Abstract

The term “glioma” refers to a group of tumors of glial cell origin of the central nervous system (CNS) including astrocytomas, oligodendrogliomas, ependymomas and other less common mixed tumors such as oligoastrocytomas. Collectively, they constitute the most common primary intraparenchymal neoplasms of the CNS. Recently, the Central Brain Tumor Registry of the United States obtained data regarding the incidence of brain tumors in the United States, from 1990 to 1994, including reports on all cases of primary CNS tumors [1]. A total of 20,765 tumors were reported in a population of 33 million, which represents approximately 14 % of the United States population. According to histologic type, the most frequently reported neoplasms were the astrocytic tumors, which accounted for 36.3 % of the total cases reported (22.6 % glioblastomas and 13.7 % astrocytomas including anaplastic astrocytomas). Oligodendrogliomas and ependymomas were less common brain tumors accounting for 3.2 % and 2.3 % of all primary CNS neoplasms, respectively.

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References

  1. Surawicz TS, Bridget J, McCarthy BJ, Kupelian V, Jukich PJ, Bruner JM, Davies FG and the Collaborating Registries of the Central Brain Tumor Registry of the United States (1999) Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States. Neurooncology 1:14–25

    CAS  Google Scholar 

  2. Kyritsis AP, Saya H (1993) Epidemiology, cytogenetics, and molecular biology of brain tumors. Curr Opin Oncol 5:474–480

    Article  PubMed  CAS  Google Scholar 

  3. Kleihues P, Burger PC, Scheithauer BW (1993) The new WHO classification of brain tumors. Brain Pathol 3:255–268

    Article  PubMed  CAS  Google Scholar 

  4. Burger PC, Green SB (1987) Patient age, histologic features and length of survival in patients with glioblastoma multiforme. Cancer 59:1617–1625

    Article  PubMed  CAS  Google Scholar 

  5. Louis DN, Cavenee WK (1997) Molecular biology of central nervous system neoplasms. In: De Vita VT, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology. Lippincott/Raven, Philadelphia, pp 2013–2022

    Google Scholar 

  6. Morgan DO (1995) Principles of CDK regulation. Nature 374:131–134

    Article  PubMed  CAS  Google Scholar 

  7. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshmann K, Tavtigian SV, Stockert E, Day RD, Johnson BE, Skolnick MH (1994) A cell cycle regulator potentially involved in the genesis of many tumor types. Science 264:436–440

    Article  PubMed  CAS  Google Scholar 

  8. Nishikawa R, Furnari FB, Lin H, Arap W, Berger MS, Cavenee WK, Su Huang HJ (1995) Loss of p16INK4 expression is frequent in high grade gliomas. Cancer Res 55:1941–1945

    PubMed  CAS  Google Scholar 

  9. Moulton T, Samara G, Chung WY, Yuan L, Desai R, Sisti M, Bruce J, Tycko B (1995) MTS 1/p 16/CDKN2lesions in primary glioblastomas multiforme. Am J Pathol 146:613–619

    PubMed  CAS  Google Scholar 

  10. Biermat W, Tohma Y, Yonekawa Y, Kleihues P, Ohgaki H (1997) Alterations of cell cycle regulatory genes in primary (de novo) and secondary glioblastomas. Acta Neuropathol 94:303–309

    Article  Google Scholar 

  11. Kyritsis AP, Zhang B, Zhang W, Xiao M, Takeshima H, Bondy ML, Cunningham JE, Levin VA, Bruner J (1996) Mutations of the p16 gene in gliomas. Oncogene 12:63–67

    PubMed  CAS  Google Scholar 

  12. Jen JJ, Harper JW, Bigner SH, Bigner DD, Papadopoulos N, Markowitz S, Wilson JK, Kinzler K, Vogelstein B (1994) Deletion of p 16 and p15 genes in brain tumors. Cancer Res 54:6353–6358

    PubMed  CAS  Google Scholar 

  13. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81:323–330

    Article  PubMed  CAS  Google Scholar 

  14. Gomez-Manzano C, Fueyo J, Kyritsis AP, Steck PA, Roth JA, McDonnell TJ, Steck KD, Levin VA, Yung WK (1996) Adenovirus-mediated transfer of the p53 gene produces rapid and generalized death of human glioma cells via apoptosis. Cancer Res 56:694–699

    PubMed  CAS  Google Scholar 

  15. Weber RG, Sabel M, Reifernberger J, Sommer C, Oberstraß J, Reifernberger G, Kiessling M, Cremer T (1996) Characterization of genomic alterations associated with glioma progression by comparative genomic hybridization. Oncogene 13:983–994

    PubMed  CAS  Google Scholar 

  16. Kyritsis AP, Xu RS, Bondy ML, Levin VA, Bruner JM (1996) Correlation of p53 immunoreactivity and sequencing in patients with glioma. Mol Carcinog 15:1–4

    Article  PubMed  CAS  Google Scholar 

  17. Watanabe K, Tachibana O, Sato K, Yonekawa Y, Kleihues P, Ohgaki H (1996) Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6:217–224

    Article  PubMed  CAS  Google Scholar 

  18. Watanabe K, Sato K, Biernat W, Tachibana O, von Ammon K, Ogata N, Yonekawa Y, Kleihues P, Ohgaki H (1997) Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clin Cancer Res 3:523–530

    PubMed  CAS  Google Scholar 

  19. Kyritsis AP, Bondy ML, Xiao M, Bernan EL, Cunningham JE, Lee PS, Levin VA, Saya H (1994) Germline p53 gene mutations in subsets of glioma patients. J Natl Cancer Inst 86:344–349

    Article  PubMed  CAS  Google Scholar 

  20. Van Meyel DJ, Ramsay DA, Chambers AF, Macdonald DR, Cairnross JG (1994) Absence of hereditary mutations in exons 5 through 9 of the p53 gene and exon 24 of the neurofibrin gene in families with glioma. Ann Neurol 35:120–122

    Article  PubMed  Google Scholar 

  21. Li YJ, Sanson M, Hoang-Huan K, Delattre J-Y, Poisson M, Thomas G, Hamelin R (1995) Incidence of germline p53 mutations in patients with gliomas. Int J Cancer 64:383–387

    Article  PubMed  CAS  Google Scholar 

  22. Reifenberger G, Ichimura K, Reifenberger J, Elkahloun AG, Meltzer PS, Collins VP (1996) Refined mapping of 12q13-q15 amplicons in malignant gliomas suggests CDK4/SAS and MDM 2 as independent amplification targets. Cancer Res 56:5141–5145

    PubMed  CAS  Google Scholar 

  23. Hecht BK, Turc-Carel C, Chatel M, Grellier P, Gioanni J, Attias R, Caudray P, Hecht F (1995) Cytogenetics of malignant gliomas: the autosomes with reference to rearrangements. Cancer Genet Cytogenet 84:1–8

    Article  PubMed  CAS  Google Scholar 

  24. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang S, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner S, Giovanella B, Ittman M, Tycko B, Hibshoosh H, Wigler M, Parsons R (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer. Science 274:1943–1947

    Article  Google Scholar 

  25. Wechsler DS, Shelly CA, Petroff CA, Dang CV (1997) MXI1, a putative suppressor gene, suppresses growth of human glioblastoma cells. Cancer Res 57:4905–4912

    PubMed  CAS  Google Scholar 

  26. Mollennhauer J, Weimann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A, Poustka A (1997) DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3–26.1 is deleted in malignant brain tumors. Nat Genet 17:32–39

    Article  Google Scholar 

  27. Rasheed BKA, Stenzel TT, McLendon RE, Parsons R, Friedman AH, Friedman HS, Bigner DD, Bigner SH (1997) PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57:4187–4190

    PubMed  CAS  Google Scholar 

  28. Tohma Y, Gratas C, Biernat W, Peraud A, Fukuda M, Yonekawa Y, Kleihues P, Ohgaki H (1998) PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas. J Neuropathol Exp Neurol 57:684–689

    Article  PubMed  CAS  Google Scholar 

  29. Reyes-Mugica M, Rieger-Christ K, Ohgaki H, Ekstrand BC, Helie M, Kleinman G, Yahanda A, Fearon ER, Kleihues P, Reale MA (1997) Loss of DCC expression and glioma progression. Cancer Res 57:382–386

    PubMed  CAS  Google Scholar 

  30. Schlegel J, Merdes A, Stumm G, Albert FK, Forsting M, Hynes N, Kiessling M (1994) Amplification of the epidermal growth factor receptor gene correlates with different growth behavior in human glioblastoma. Int J Cancer 56:72–77

    Article  PubMed  CAS  Google Scholar 

  31. Schwechheimer K, Huang S, Cavenee WK (1995) EGFR gene amplification-rearrangements in human glioblastomas. Int J Cancer 62:145–148

    Article  PubMed  CAS  Google Scholar 

  32. Lang FF, Miller DC, Koslow M, Newcomb EW (1994) Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J Neurosurg 81:427–436

    Article  PubMed  CAS  Google Scholar 

  33. Hayashi Y, Ueki K, Waha A, Wiestler OD, Louis DN, von Deimling A (1997) Association of EGFR gene amplification and CDKN2 (p 16/MTS 1) gene deletion in glioblastoma multiforme. Brain Pathol 7:871–875

    Article  PubMed  CAS  Google Scholar 

  34. Hurtt MR, Moossy J, Donovan PM, Locker J (1992) Amplification of epidermal growth factor receptor gene in gliomas: histopathology and prognosis. J Neuropathol Exp Neurol 51:84–90

    Article  PubMed  CAS  Google Scholar 

  35. Yamada N, Kato M, ten Dijke P, Yamashita H, Sampath TK, Heldin C-H,Miyazono K, Funa K (1996) Bone morphogenetic protein type 1B receptor is progressively expressed in malignant glioma tumors. Br J Cancer 73:624–629

    CAS  Google Scholar 

  36. Fakhrai H, Dorigo O, Shawler DL, Lin H, Mercola D, Black KL, Royston I, Sobol RE (1996) Eradication of established intracranial rat glioma,as by transforming growth factor ββ antisense gene therapy. Proc Natl Acad Sci USA 93:2909–2914

    Article  PubMed  CAS  Google Scholar 

  37. Hermanson M, Funa K, Koopmann J, Maintz D, Waha A, Westermark B, Heldin C-H, Wiestler OD, Louis DN, von Deimling A, Nister M (1996) Association of high plateletderived growth factor (PDGF) á receptor expression with loss of heterozygosity (LOH) on chromosome 17p in human malignant gliomas. Cancer Res 56:164–171

    PubMed  CAS  Google Scholar 

  38. Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tunmor angiogenesis factor in human gliomas. Nature 359:845–848

    Article  PubMed  CAS  Google Scholar 

  39. Segal DH, Germano IM, Bederson JB (1997) Effects of basic fibroblast growth factor on in vivo cerebral tumorigenesis in rats. Neurosurgery 40:1027–1033

    Article  PubMed  CAS  Google Scholar 

  40. Yamaguchi F, Saya H, Bruner JM, Morrison RS (1994) Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas. Proc Natl Acad Sci USA 91:484–488

    Article  PubMed  CAS  Google Scholar 

  41. Litofski NS, Hinton D, Raffel C (1994) The lack of a role for p53 in astrocytomas in pediatric patients. Neurosurgery 34:967–972

    Article  Google Scholar 

  42. von Deimling A, Louis DN, von Ammon K, Petersen I, Hoell T, Chung RY, Martuza RL, Schoenfeld DA, Yasargil MG, Wiestler OD, Seizinger BR (1992) Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J Neurosurg 77:295–301

    Article  Google Scholar 

  43. Platten M, Giordano MJ, Dirven CM, Gutmann DH, Louis DN (1996) Up-regulation of specific NF 1 gene transcripts in sporadic pilocytic astrocytomas. Am J Pathol 149:621–627

    PubMed  CAS  Google Scholar 

  44. Paulus W, Lisle DK, Tonn JC, Wolf HK, Roggendorf W, Reeves SA, Louis DN (1996) Molecular genetic alterations in pleomorphic xanthoastrocytoma. Acta Neuropathol 91:293–297

    Article  PubMed  CAS  Google Scholar 

  45. Louis DN, von Deimling A, Dickersin GR, Dooling EC, Seizinger BR (1992) Desmoplastic cerebral astrocytomas of infancy: a histopathologic, immunohistochemical, ultrastructural, and molecular genetic study. Hum Pathol 23: 1402–1409

    Article  PubMed  CAS  Google Scholar 

  46. Shaw EG, Scheithauer BW, O’Fallon JR, Tazelaar HP, Davis DH (1992) Oligodendrogliomas: the Mayo Clinic experience. J Neurosurg 76:428–434

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  48. Paleologos NA, Cairncross J (1999) Treatment of oligodendroglioma: an update. Neurooncology 1:61–68

    CAS  Google Scholar 

  49. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP (1994) Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1 p. Am J Pathol 145:1175–1190

    PubMed  CAS  Google Scholar 

  50. Wu JK, Folkerth RD, Ye Z, Darras BT (1993) Aggressive oligodendroglioma predicted by chromosome 10 restriction fragment length polymorphism analysis. Case study. J Neurooncol 15:29–35

    Article  CAS  Google Scholar 

  51. Reifenberger J, Reifenberger G, Ichimura K, Schmidt EE, Wechsler W, Collins VP (1996) Epidermal growth factor receptor expression in oligodendroglial tumors. Am J Pathol 149:29–35

    PubMed  CAS  Google Scholar 

  52. Ernestus RI, Schroder R, Stutzer H, Klug N (1996) Prognostic relevance of localization and grading in intracranial ependymomas of childhood. Childs Nerv Syst 12:522–526

    Article  PubMed  CAS  Google Scholar 

  53. Gerszten PC, Pollack IF, Martinez AJ, Lo KH, Janosky J, Albright AL (1996) Intracranial ependymomas of childhood-lack of correlation of histopathology and clinical outcome. Pathol Res Pract 192:515–522

    Article  PubMed  CAS  Google Scholar 

  54. Sala F, Talacchi A, Mazza C, Prisco R, Ghimenton C, Bricolo A (1998) Prognostic factors in childhood intracranial ependymomas: the role of age and tumor location. Pediatr Neurosurg 28:135–142

    Article  PubMed  CAS  Google Scholar 

  55. Rogatto SR, Casartelli C, Rainho CA, Barbieri-Neto J (1993) Chromosomes in the genesis and progression of ependymomas. Cancer Genet Cytogenet 69:146–152

    Article  PubMed  CAS  Google Scholar 

  56. Ebert C, von Haken M, Meyer-Puttlitz B, Wiestler OD, Reifebenberger G, Pietsch T, von Deimling A (1999) Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas. Am J Pathol 155:627–632

    Article  PubMed  CAS  Google Scholar 

  57. von Haken MS, White EC, Daneshvar-Shyesther L, Sih S, Choi E, Kalra R, Cogen PH (1996) Molecular genetic analysis of chromosome arm 17p and chromosome arm 22q DNA sequences in sporadic pediatric ependymomas. Genes Chromosomes Cancer 17:37–44

    Article  Google Scholar 

  58. Fink KL, Rushing EJ, Schold SC Jr, Nisen PD (1996) Infrequency of p53 gene mutations in ependymomas. J Neuroonco127:111–115

    Google Scholar 

  59. Griffin CA, Long PP, Carson BS, Brem H (1992) Chromosome abnormalities in low-grade central nervous system tumors. Cancer Genet Cytogenet 60:67–73

    Article  PubMed  CAS  Google Scholar 

  60. Bijlsma EK, Voesten AM, Bijleveld EH, Troost D, Westerveld A, Merel P, Thomas G, Hulsebos TJ (1995) Molecular analysis of genetic changes in ependymomas. Genes Chromosomes Cancer 13:272–277

    Article  PubMed  CAS  Google Scholar 

  61. Kraus JA, Koopman J, Kaskel P, Maintz D, Brandner S, Schramm J, Louis DN, Wiestler OD, von Deimling A (1995) Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropathol Exp Neurol 54:91–95

    Article  PubMed  CAS  Google Scholar 

  62. Maintz D, Fiedler K, Koopmann J, Rollbrocker B, Nechev S, Lenartz D, Stangl AP, Louis DN, Schramm J, Wiestler OD, von Deimling A (1997) Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol Exp Neurol 56:1098–1104

    Article  PubMed  CAS  Google Scholar 

  63. Bigner SH, Rasheed BKA, Wiltshire R, McLendon RE (1999) Morphologic and molecular genetic aspects of oligodendroglial neoplasms. Neurooncology 1:52–60

    CAS  Google Scholar 

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Authors
  1. A. C. Goussia
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  2. K. Polyzoidis
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  3. A. P. Kyritsis
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  1. Radiology Department, AHEPA University Hospital, Thessaloniki, Greece

    Antonios Drevelegas MD

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Goussia, A.C., Polyzoidis, K., Kyritsis, A.P. (2002). Molecular Abnormalities in Gliomas. In: Drevelegas, A. (eds) Imaging of Brain Tumors with Histological Correlations. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04951-8_3

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  • DOI: https://doi.org/10.1007/978-3-662-04951-8_3

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