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Toxicologic Pathology, Vol. 28, No. 1, 164-170 (2000)
DOI: 10.1177/019262330002800121

Phenotype vs Genotype in the Evolution of Astrocytic Brain Tumors

Paul Kleihues

International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France

Hiroko Ohgaki

International Agency for Research on Cancer, World Health Organization, 69372 Lyon, France

Astrocytic brain tumors are the most frequent human gliomas and they include a wide range of neoplasms with distinct clinical, histopathologic, and genetic features. Diffuse astrocytomas are predominantly located in the cerebral hemispheres of adults and have an inherent tendency to progress to anaplastic astrocytoma and (secondary) glioblastoma. The majority of glioblastomas develop de novo (primary glioblastomas), without an identifiable less-malignant precursor lesion. These subtypes of glioblastoma evolve through different genetic pathways, affect patients at different ages, and are likely to differ in their responses to therapy. Primary glioblastomas occur in older patients and typically show epidermal growth factor receptor (EGFR) overexpression, PTEN mutations, p16 deletions, and, less frequently, MDM2 amplification. Secondary glioblastomas develop in younger patients and often contain TP53 mutations as their earliest detectable alteration. Morphologic variants of glioblastoma were shown to have intermediate clinical and genetic profiles. The giant cell glioblastoma clinically and genetically occupies a hybrid position between primary (de novo) and secondary glioblastomas. Gliosarcomas show identical gene mutations in the gliomatous and sarcomatous tumor components, which strongly supports the concept that there is a monoclonal origin for gliosarcomas and an evolution of the sarcomatous component due to aberrant mesenchymal differentiation in a highly malignant astrocytic neoplasm.

Key Words: Primary glioblastoma • secondary glioblastoma • glioma progression • giant cell glioblastoma • gliosarcoma • p53 • EGFR • PTEN • p16 • MDM2

References

  • Barak Y., Gottlieb E., Juven Gershon T, Oren M. ( 1994). Regulation of mdm2 expression by p53: Alternative promoters produce transcripts with nonidentical translation potential. Genes Dev 8: 1739-1749.[Abstract/Free Full Text]
  • Barker FG II, Davis RL, Chang SM, Prados MD (1996). Necrosis as a prognostic factor in glioblastoma multiforme. Cancer 77: 1161-1166.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Biernat W., Aguzzi A., Sure U., Grant JW, Kleihues P., Hegi ME ( 1995). Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous components of gliosarcomas suggest a common origin from glial cells. J Neuropathol Exp Neurol 54: 651-656.[ISI][Medline] [Order article via Infotrieve]
  • Biernat W., Hegi M., Aguzzi A., Kleihues P. (1997). Gliosarcoma. In: Pathology and Genetics of Tumours of the Nervous System, Vol 1, Kleihues P, Cavenee WK (eds). International Agency for Research on Cancer, Lyon, France, pp 27-28.
  • Biernat W., Kleihues P., Yonekawa Y., Ohgaki H. (1997). Amplification and overexpression of MDM2 in primary (de novo) glioblastomas. J Neuropathol Exp Neurol 56: 180-185.[ISI][Medline] [Order article via Infotrieve]
  • Biernat 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.[CrossRef][Medline] [Order article via Infotrieve]
  • Boerman RH, Anderl K., Herath J., Borell T., Johnson N., Schaeffer-Klein J., Kirchhof A., Raap AK, Scheithauer BW, Jenkins RB (1996). The glial and mesenchymal elements of gliosarcomas share similar genetic alterations. J Neuropathol Exp Neurol 55: 973-981.[ISI][Medline] [Order article via Infotrieve]
  • Boström J., Cobbers Jmjl, Wolter M., Tabatabai G., Weber RG, Lichter P., Collins VP, Reifenberger G. (1998). Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q. Cancer Res 58: 29-33.[Abstract/Free Full Text]
  • Burger PC, Green SB (1987). Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59: 1617-1625.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Burger PC, Scheithauer BW (1994). Tumors of the Central Nervous System. Armed Forces Institute of Pathology, Washington, DC.
  • Burns KL, Ueki K., Jhung SL, Koh J., Louis DN (1998). Molecular genetic correlates of p16, cdk4, and pRb immunohistochemistry in glioblastomas. J Neuropathol Exp Neurol 57: 122-130.[ISI][Medline] [Order article via Infotrieve]
  • Claesson Welsh L. (1994). Platelet-derived growth factor receptor signals. J Biol Chem 269: 32023-32026.[Free Full Text]
  • Dropcho EJ, Soong SJ (1996). The prognostic impact of prior low grade histology in patients with anaplastic gliomas: A case-control study. Neurology 47: 684-690.[Abstract/Free Full Text]
  • Duerr EM, Rollbrocker B., Hayashi Y., Peters N., Meyer-Puttlitz B., Louis DN, Schramm J., Wiestler OD, Parsons R., Eng C., von Deimling A. (1998). PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16: 2259-2264.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ekstrand AJ, Sugawa N., James CD, Collins VP (1992). Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci USA 89: 4309-4313.[Abstract/Free Full Text]
  • Fujisawa H., Kurrer M., Reis RM, Yonekawa Y., Kleihues P., Ohgaki H. (1999). Acquisition of the glioblastoma phenotype during astrocytoma progression is associated with LOH on chromosome 10q25-qter. Am J Pathol 155: 387-394.[Abstract/Free Full Text]
  • Fults D., Pedone C. (1993). Deletion mapping of the long arm of chromosome 10 in glioblastoma multiforme. Genes Chromosomes Cancer 7: 173-177.[ISI][Medline] [Order article via Infotrieve]
  • Haffner R., Oren M. ( 1995). Biochemical properties and biological effects of p53. Curr Opin Genet Dev 5: 84-90.[CrossRef][Medline] [Order article via Infotrieve]
  • Hainaut P. (1995). The tumor suppressor protein p53: A receptor to genotoxic stress that controls cell growth and survival. Curr Opin Oncol 7: 76-82.[Medline] [Order article via Infotrieve]
  • Hayashi Y., Ueki K., Waha A., Wiestler OD, Louis DN, von Deimling A. (1997). Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme. Brain Pathol 7: 871-875.[ISI][Medline] [Order article via Infotrieve]
  • Heldin CH, Westermark B. (1990). Platelet-derived growth factor: Mechanism of action and possible in vivo function. Cell Regul 1: 555-566.[ISI][Medline] [Order article via Infotrieve]
  • Hermanson M., Funa K., Koopmann J., Maintz D., Waha A., Westermark B., Heldin CH, Wiestler OD, Louis DN, von Deimling A., Nister M. (1996). Association of loss of heterozygosity on chromosome 17p with high platelet-derived growth factor alpha receptor expression in human malignant gliomas. Cancer Res 56: 164-171.[Abstract/Free Full Text]
  • Kinzler KW, Vogelstein B. (1998). Landscaping the cancer terrain. Science 280: 1036-1037.[Free Full Text]
  • Kleihues P., Burger PC, Scheithauer BW (1993). The new WHO classification of brain tumours. Brain Pathol 3: 255-268.[ISI][Medline] [Order article via Infotrieve]
  • Kleihues P., Ohgaki H. (1997). Genetics of glioma progression and the definition of primary and secondary glioblastoma. Brain Pathol 7: 1131-1136.[ISI]
  • Kleihues P., Ohgaki H. (1999). Primary and secondary glioblastomas: From concept to clinical diagnosis. Neuro- Oncology 1: 44-51.[CrossRef]
  • Korkolopoulou P., Christodoulou P., Kouzelis K., Hadjiyannakis M., Priftis A., Stamoulis G., Seretis A., Thomas-Tsagli E. (1997). MDM2 and p53 expression in gliomas: A multivariate survival analysis including proliferation markers and epidermal growth factor receptor. Br J Cancer 75: 1269-1278.[ISI][Medline] [Order article via Infotrieve]
  • 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.[ISI][Medline] [Order article via Infotrieve]
  • Lantos PL, VandenBerg SR, Kleihues P. (1996). Tumours of the nervous system. In: Greenfield's Neuropathology, Vol 9, Graham DI, Lantos PL (eds). Edward Arnold, London, pp 583-879.
  • Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang SI, Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner SH, Giovanella BC, Ittmann M., Tycko B., Hibshoosh H., Wigler MH, Parsons R. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943-1947.[Abstract/Free Full Text]
  • Libermann TA, Nusbaum HR, Razon N., Kris R., Lax I., Soreq H., Whittle N., Waterfield MD, Ullrich A., Schlessinger J. (1985). Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313: 144-147.[CrossRef][Medline] [Order article via Infotrieve]
  • Louis DN (1994). The p53 gene and protein in human brain tumors. J Neuropathol Exp Neurol 53: 11-21.[ISI][Medline] [Order article via Infotrieve]
  • Louis DN, Gusella JF (1995). A tiger behind many doors: Multiple genetic pathways to malignant glioma. Trends Genet 11: 412-415.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Louis DN, von Deimling A., Chung RY, Rubio MP, Whaley JM, Eib1 RH, Ohgaki H., Wiestler OD, Thor AD, Seizinger BR (1993). Comparative study of p53 gene and protein alterations in human astrocytic tumors. J Neuropathol Exp Neurol 52: 31-38.[ISI][Medline] [Order article via Infotrieve]
  • Matsumoto R., Tada M., Nozaki M., Zhang CL, Sawamura Y., Abe H. (1998). Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms. Cancer Res 58: 609-613.[Abstract/Free Full Text]
  • Meyer-Puttlitz B., Hayashi Y., Waha A., Rollbrocker B., Bostrom J., Wiestler OD, Louis DN, Reifenberger G., von Deimling A. (1997). Molecular genetic analysis of giant cell glioblastomas. Am J Pathol 151: 853-857.[Abstract]
  • Mollenhauer J., Wiemann 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 tumours. Nat Genet 17: 32-39.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Nagane M., Coufal F., Lin H., Bogler O., Cavenee WK, Huang HJ (1996). A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res 56: 5079-5086.[Abstract/Free Full Text]
  • Nelson JS, Tsukada Y., Schoenfeld D., Fulling K., Lamarche J., Peress N. (1983). Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas. Cancer 52: 550-554.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Newcomb EW, Cohen H., Lee SR, Bhalla SK, Bloom J., Hayes RL, Miller DC (1998). Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes. Brain Pathol 8: 655-667.[ISI][Medline] [Order article via Infotrieve]
  • Newcomb EW, Madonia WJ, Pisharody S., Lang FF, Koslow M., Miller DC (1993). A correlative study of p53 protein alteration and p53 gene mutation in glioblastoma multiforme. Brain Pathol 3: 229-235.[ISI][Medline] [Order article via Infotrieve]
  • Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R., Cleary K., Bigner SH, Davidson N., Baylin S., Devilee P., Glover T., Collins FS, Weston A., Modali R., Harris CC, Vogelstein B. (1989). Mutations in the p53 gene occur in diverse human tumour types. Nature 342: 705-708.[CrossRef][Medline] [Order article via Infotrieve]
  • Nishikawa R., Ji XD, Harmon RC, Lazar CS, Gill GN, Cavenee WK, Huang HJ (1994). A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci USA 91: 7727-7731.[Abstract/Free Full Text]
  • Ohgaki H., Schauble B., zur Hausen A., von Ammon K., Kleihues P. (1995). Genetic alterations associated with the evolution and progression of astrocytic brain tumours. Virchows Arch 427: 113-118.[ISI][Medline] [Order article via Infotrieve]
  • Olson DC, Marechal V., Momand J., Chen J., Romocki C., Levine AJ (1993). Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene 8: 2353-2360.[ISI][Medline] [Order article via Infotrieve]
  • Palma L., Celli P., Maleci A., Di Lorenzo N., Cantore G. (1989). Malignant monstrocellular brain tumours. A study of 42 surgically treated cases. Acta Neurochir ( Wien) 97: 17-25.[CrossRef][Medline] [Order article via Infotrieve]
  • Peraud A., Watanabe K., Plate KH, Yonekawa Y., Kleihues P., Ohgaki H. (1997). p53 Mutations versus EGF receptor expression in giant cell glioblastomas. J Neuropathol Exp Neurol 56: 1235-1241.
  • Picksley SM, Lane DP (1993). The p53-mdm2 autoregulatory feedback loop: A paradigm for the regulation of growth control by p53? Bioessays 15: 689-690.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Pomerantz J., Schreiber-Agus N., Liegeois NJ, Silverman A., Alland L., Chin L., Potes J., Chen K., Orlow I., Lee HW, Cordon-Cardo C., DePinho RA (1998). The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 92: 713-723.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ponten J., Adami HO, Friberg LG, Gustafsson L., Miller AB, Parkin M., Sparen P., Trichopoulos D. (1995). HPV and cervical cancer. Int J Cancer 63: 317.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Prigent SA, Nagane M., Lin H., Huvar I., Boss GR, Feramisco JR, Cavenee WK, Huang HS (1996). Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras-Shc-Grb2 pathway. J Biol Chem 271: 25639-25645.[Abstract/Free Full Text]
  • Rasheed BK, 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.[Abstract/Free Full Text]
  • Reifenberger G., Liu L., Ichimura K., Schmidt EE, Collins VP (1993). Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res 53: 2736-2739.[Abstract/Free Full Text]
  • Reifenberger J., Ring GU, Gies U., Cobbers L., Oberstrass J., An HX, Niederacher D., Wechsler W., Reifenberger G. (1996). Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression. J Neuropathol Exp Neurol 55: 822-831.[ISI][Medline] [Order article via Infotrieve]
  • Reis RM, Konu-Lebleblicioglu D., Lopes JM, Kleihues P., Ohgaki H. (1999). Genetic profile of the gliosarcoma. Am J Pathol (in press).
  • Russell DS, Rubinstein LJ (1989). Pathology of Tumours of the Nervous System. Edward Arnold, London.
  • Scherer HJ (1940). Cerebral astrocytomas and their derivatives. Am J Cancer 40: 159-198.
  • Sidransky D., Mikkelsen T., Schwechheimer K., Rosenblum ML, Cavenee WK, Vogelstein B. (1992). Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature 355: 846-847.[CrossRef][Medline] [Order article via Infotrieve]
  • Sigalas I., Calvert AH, Anderson JJ, Neal DE, Lunec J. (1996). Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: Transforming ability and frequent detection in human cancer. Nat Med 2: 912-917.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Somerville Rpt, Shoshan Y., Eng C., Barnett G., Miller D., Cowell JK (1998). Molecular analysis of two putative tumour suppressor genes, PTEN and DMBT, which have been implicated in glioblastoma multiforme disease progression. Oncogene 17: 1755-1757. 61. Sonoda Y., Murakami Y., Tominaga T., Kayama T., Yoshimoto T., Sekiya T. (1996). Deletion mapping of chromosome 10 in human glioma. Jpn J Cancer Res 87: 363-367.[CrossRef][ISI]
  • Steck PA, Ligon AH, Cheong P., Yung WK, Pershouse MA (1995). Two tumor suppressive loci on chromosome 10 involved in human glioblastomas. Genes Chromosomes Cancer 12: 255-261.[ISI][Medline] [Order article via Infotrieve]
  • Steck PA, Pershouse MA, Jasser SA, Yung Wka, Lin H., Ligon AH, Langford LA, Baumgard ML, Hattier T., Davis T., Frye C., Hu R., Swedlund B., Teng Dhf, Tavtigian SV (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15: 356-362.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Sugawa N., Ekstrand AJ, James CD, Collins VP (1990). Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci USA 87: 8602-8606.[Abstract/Free Full Text]
  • 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.[ISI][Medline] [Order article via Infotrieve]
  • Tohma Y., Gratas C., Van Meir EG, Desbaillets I., Tenan M., Tachibana O., Kleihues P., Ohgaki H. (1998). Necrogenesis and Fas/APO-1(CD95) expression in primary (de novo) and secondary glioblastomas. J Neuropathol Exp Neurol 57: 239-245.[ISI][Medline] [Order article via Infotrieve]
  • Ueki K., Ono Y., Henson JW, Efird JT, von Deimling A., Louis DN (1996). CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res 56: 150-153.[Abstract/Free Full Text]
  • Vogelstein B., Kinzler KW (1993). The multistep nature of cancer. Trends Genet 9: 138-141.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • 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.[ISI][Medline] [Order article via Infotrieve]
  • von Deimling A., Louis DN, von Ammon K., Petersen I., Wiestler OD, Seizinger BR (1992). Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas. Cancer Res 52: 4277-4279. 71. von Deimling A., Nagel J., Bender B., Lenartz D., Schramm J., Louis DN, Wiestler OD (1994). Deletion mapping of chromosome 19 in human gliomas. Int J Cancer 57: 676-680.[ISI][Medline] [Order article via Infotrieve]
  • von Deimling A., von Ammon K., Schoenfeld D., Wiestler OD, Seizinger BR, Louis DN (1993). Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol 3: 19-26.[Medline] [Order article via Infotrieve]
  • Wang SI, Puc J., Li J., Bruce JN, Cairns P., Sidransky D., Parsons R. (1997). Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res 57: 4183-4186.[Abstract/Free Full Text]
  • 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.[Abstract]
  • 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.[ISI][Medline] [Order article via Infotrieve]
  • 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: 2965-2969.[Abstract/Free Full Text]
  • Zauberman A., Flusberg D., Haupt Y., Barak Y., Oren M. (1995). A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res 23: 2584-2592.[Abstract/Free Full Text]
  • Zhang Y., Xiong Y., Yarbrough WG (1998). ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92: 725-734.[CrossRef][ISI][Medline] [Order article via Infotrieve]

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