Skip to main content

Advertisement

SpringerLink
Log in

Mouse models of CNS embryonal tumors

  • Review Article
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

Central nervous system (CNS) embryonal tumors are devastating cancers in children, consisting of medulloblastomas, CNS primitive neuroectodermal tumors, and atypical teratoid/rhabdoid tumors. One of the reasons that CNS embryonal tumors remain difficult to treat is their rarity, which makes conducting clinical trials for these tumors difficult. Recent advances of molecular biology have led us to identify molecular and genetic causality of brain tumors. Based on the genetic alterations found in humans, multiple models of human CNS embryonal tumors have been generated in genetically engineered mice. These mouse models are valuable tools for understanding brain tumor biology and discovering novel therapeutic targets and drugs. In this article, we review molecular and cytogenetic characteristics of human CNS embryonal tumors and corresponding mouse models that have been developed. These findings indicate that common genetic abnormalities are seen in variants of human CNS embryonal tumors, and multiple histological variants of these tumors can be generated from a single set of genetic abnormalities in mice. These data provide insight into the biology and classification of CNS embryonal tumors.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Louis DN, Ohgaki H, Wiestler OD, et al (eds) Tumours of the central nervous system. World Health Organization Classification of Tumours. IARC, Lyon, pp 132–149

  2. Bigner SH, Mark J, Friedman HS, Biegel JA, et al (1988) Structural chromosomal abnormalities in human medulloblastoma. Cancer Genet Cytogenet 30:91–101

    Article  CAS  PubMed  Google Scholar 

  3. Griffin CA, Hawkins AL, Packer RJ, et al (1988) Chromosome abnormalities in pediatric brain tumors. Cancer Res 48:175–180

    CAS  PubMed  Google Scholar 

  4. James CD, He J, Carlbom E, et al (1990) Loss of genetic information in central nervous system tumors common to children and young adults. Genes Chromosomes Cancer 2:94–102

    Article  CAS  PubMed  Google Scholar 

  5. Saylors RL III, Sidransky D, Friedman HS, et al (1991) Infrequent p53 gene mutations in medulloblastomas. Cancer Res 51:4721–4723

    PubMed  Google Scholar 

  6. Cogen PH, Daneshvar L, Metzger AK, et al (1992) Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis. Am J Hum Genet 50:584–589

    CAS  PubMed  Google Scholar 

  7. Badiali M, Iolascon A, Loda M, et al (1993) p53 gene mutations in medulloblastoma. Immunohistochemistry, gel shift analysis, and sequencing. Diagn Mol Pathol 2:23–28

    CAS  PubMed  Google Scholar 

  8. McDonald JD, Daneshvar L, Willert JR, et al (1994) Physical mapping of chromosome 17p13.3 in the region of a putative tumor suppressor gene important in medulloblastoma. Genomics 23:229–232

    Article  CAS  PubMed  Google Scholar 

  9. Reardon DA, Michalkiewicz E, Boyett JM, et al (1997) Extensive genomic abnormalities in childhood medulloblastoma by comparative genomic hybridization. Cancer Res 57:4042–4047

    CAS  PubMed  Google Scholar 

  10. Nicholson JC, Ross FM, Kohler JA, et al (1999) Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours. Br J Cancer 80:1322–1331

    Article  CAS  PubMed  Google Scholar 

  11. Gilbertson R, Wickramasinghe C, Hernan R, et al (2001) Clinical and molecular stratification of disease risk in medulloblastoma. Br J Cancer 85:705–712

    Article  CAS  PubMed  Google Scholar 

  12. Lamont JM, McManamy CS, Pearson AD, et al (2004) Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clin Cancer Res 10:5482–5493

    Article  CAS  PubMed  Google Scholar 

  13. Rood BR, Zhang H, Weitman DM, et al (2002) Hypermethylation of HIC-1 and 17p allelic loss in medulloblastoma. Cancer Res 62:3794–3797

    CAS  PubMed  Google Scholar 

  14. Waha A, Waha A, Koch A, et al (2003) Epigenetic silencing of the HIC-1 gene in human medulloblastomas. J Neuropathol Exp Neurol 62:1192–1201

    CAS  PubMed  Google Scholar 

  15. Lindsey JC, Anderton JA, Lusher ME, et al (2005) Epigenetic events in medulloblastoma development. Neurosurg Focus 19: E10

    Article  PubMed  Google Scholar 

  16. Frank AJ, Hernan R, Hollander A, et al (2004) The TP53-ARF tumor suppressor pathway is frequently disrupted in large/cell anaplastic medulloblastoma. Brain Res Mol Brain Res 121: 137–140

    Article  CAS  PubMed  Google Scholar 

  17. Vorechovský I, Tingby O, Hartman M, et al (1997) Somatic mutations in the human homologue of Drosophila patched in primitive neuroectodermal tumours. Oncogene 15:361–366

    Article  PubMed  Google Scholar 

  18. Raffel C, Jenkins RB, Frederick L, et al (1997) Sporadic medulloblastomas contain PTCH mutations. Cancer Res 57:842–845

    CAS  PubMed  Google Scholar 

  19. Wolter M, Reifenberger J, Sommer C, et al (1997) Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 57:2581–2585

    CAS  PubMed  Google Scholar 

  20. Reifenberger J, Wolter M, Weber RG, et al (1998) Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 58:1798–1803

    CAS  PubMed  Google Scholar 

  21. Taylor MD, Liu L, Raffel C, Hui CC, et al (2002) Mutations in SUFU predispose to medulloblastoma. Nat Genet 31:306–310

    Article  CAS  PubMed  Google Scholar 

  22. Koch A, Waha A, Hartmann W, et al (2004) No evidence for mutations or altered expression of the Suppressor of Fused gene (SUFU) in primitive neuroectodermal tumours. Neuropathol Appl Neurobiol 30:532–539

    Article  CAS  PubMed  Google Scholar 

  23. Zurawel RH, Chiappa SA, Allen C, et al (1998) Sporadic medulloblastomas contain oncogenic beta-catenin mutations. Cancer Res 58:896–899

    CAS  PubMed  Google Scholar 

  24. Eberhart CG, Tihan T, Burger PC (2000) Nuclear localization and mutation of beta-catenin in medulloblastomas. J Neuropathol Exp Neurol 59:333–337

    CAS  PubMed  Google Scholar 

  25. Ellison DW, Onilude OE, Lindsey JC, et al (2005) Beta-catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children’s Cancer Study Group Brain Tumour Committee. J Clin Oncol 23:7951–7957

    Article  CAS  PubMed  Google Scholar 

  26. Broderick DK, Di C, Parrett TJ, et al (2004) Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res 64:5048–5050

    Article  CAS  PubMed  Google Scholar 

  27. Inda MM, Mercapide J, Muñoz J, et al (2004) PTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors. Oncol Rep 12:1341–1347

    PubMed  Google Scholar 

  28. Rasheed BK, Stenzel TT, McLendon RE, et al (1997) PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57:4187–4190

    CAS  PubMed  Google Scholar 

  29. Fan X, Mikolaenko I, Elhassan I, et al (2004) Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res 64:7787–7793

    Article  CAS  PubMed  Google Scholar 

  30. Aldosari N, Bigner SH, Burger PC, et al (2002) MYCC and MYCN oncogene amplification in medulloblastoma. A fluorescence in situ hybridization study on paraffin sections from the Children’s Oncology Group. Arch Pathol Lab Med 126:540–544

    PubMed  Google Scholar 

  31. Eberhart CG, Kratz JE, Schuster A, et al (2002) Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas. Brain Pathol 12:36–44

    Article  CAS  PubMed  Google Scholar 

  32. Rickert CH, Paulus W (2004) Comparative genomic hybridization in central and peripheral nervous system tumors of childhood and adolescence. J Neuropathol Exp Neurol 63:399–417

    CAS  PubMed  Google Scholar 

  33. Reifenberger J, Janssen G, Weber RG, et al (1998) Primitive neuroectodermal tumors of the cerebral hemispheres in two siblings with TP53 germline mutation. J Neuropathol Exp Neurol 57:179–187

    Article  CAS  PubMed  Google Scholar 

  34. Ho YS, Hsieh LL, Chen JS, et al (1996) p53 gene mutation in cerebral primitive neuroectodermal tumor in Taiwan. Cancer Lett 104:103–113

    Article  CAS  PubMed  Google Scholar 

  35. Kraus JA, Felsberg J, Tonn JC, et al (2002) Molecular genetic analysis of the TP53, PTEN, CDKN2A, EGFR, CDK4 and MDM2 tumour-associated genes in supratentorial primitive neuroectodermal tumours and glioblastomas of childhood. Neuropathol Appl Neurobiol 28:325–333

    Article  CAS  PubMed  Google Scholar 

  36. Koch A, Waha A, Tonn JC, et al (2001) Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors. Int J Cancer 93:445–449

    Article  CAS  PubMed  Google Scholar 

  37. Russo C, Pellarin M, Tingby O, et al (1999) Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors. Cancer (Phila) 86:331–339

    Article  CAS  Google Scholar 

  38. Rostomily RC, Bermingham-McDonogh O, Berger MS, et al (1997) Expression of neurogenic basic helix-loop-helix genes in primitive neuroectodermal tumors. Cancer Res 57:3526–3531

    CAS  PubMed  Google Scholar 

  39. Versteege I, Sévenet N, Lange J, et al (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature (Lond) 394:203–206

    Article  CAS  Google Scholar 

  40. Biegel JA, Zhou JY, Rorke LB, et al (1999) Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59:74–79

    CAS  PubMed  Google Scholar 

  41. Biegel JA, Tan L, Zhang F, et al (2002) Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clin Cancer Res 8:3461–3467

    CAS  PubMed  Google Scholar 

  42. Judkins AR, Mauger J, Ht A, et al (2004) Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms. Am J Surg Pathol 28:644–650

    PubMed  Google Scholar 

  43. Sévenet N, Sheridan E, Amram D et al (1999) Constitutional mutations of the hSNF5/INI1 gene predispose to a variety of cancers. Am J Hum Genet 65:1342–1348

    Article  PubMed  Google Scholar 

  44. Taylor MD, Gokgoz N, Andrulis IL, et al (2000) Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene. Am J Hum Genet 66:1403–1406

    Article  CAS  PubMed  Google Scholar 

  45. Biegel JA (2006) Molecular genetics of atypical teratoid/rhabdoid tumor. Neurosurg Focus 20:E11

    Article  PubMed  Google Scholar 

  46. Roberts CW, Orkin SH (2004) The SWI/SNF complex: chromatin and cancer. Nat Rev Cancer 4:133–142

    CAS  PubMed  Google Scholar 

  47. Vries RG, Bezrookove V, Zuijderduijn LM, et al (2005) Cancerassociated mutations in chromatin remodeler hSNF5 promote chromosomal instability by compromising the mitotic checkpoint. Genes Dev 19:665–670

    Article  CAS  PubMed  Google Scholar 

  48. Isakoff MS, Sansam CG, Tamayo P, et al (2005) Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc Natl Acad Sci U S A 102:17 745–17 750

    Article  CAS  Google Scholar 

  49. Brown HG, Kepner JL, Perlman EJ, et al (2000) ’Large cell/anaplastic’ medulloblastomas: a Pediatric Oncology Group study. J Neuropathol Exp Neurol 59:857–865

    CAS  PubMed  Google Scholar 

  50. Eberhart CG, Kepner JL, Goldthwaite PT, et al (2002) Histopathologic grading of medulloblastomas: a Pediatric Oncology Group study. Cancer (Phila) 94:552–560

    Article  Google Scholar 

  51. Ellison D (2002) Classifying the medulloblastoma: insights from morphology and molecular genetics. Neuropathol Appl Neurobiol 28:257–282

    Article  CAS  PubMed  Google Scholar 

  52. Sure U, Berghorn WJ, Bertalanffy H, et al (1995) Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute. Acta Neurochir (Wien) 132:59–65

    Article  CAS  Google Scholar 

  53. Giangaspero F, Perilongo G, Fondelli MP, et al (1999) Medulloblastoma with extensive nodularity: a variant with favorable prognosis. J Neurosurg 91:971–977

    Article  CAS  PubMed  Google Scholar 

  54. Bayani J, Zielenska M, Marrano P, et al (2000) Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping. J Neurosurg 93:437–448

    Article  CAS  PubMed  Google Scholar 

  55. Avet-Loiseau H, Vénuat AM, Terrier-Lacombe MJ, et al (1999) Comparative genomic hybridization detects many recurrent imbalances in central nervous system primitive neuroectodermal tumours in children. Br J Cancer 79:1843–1847

    Article  CAS  PubMed  Google Scholar 

  56. Inda MM, Perot C, Guillaud-Bataille M, et al (2005) Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system. Histopathology (Oxf) 47:631–637

    Article  CAS  Google Scholar 

  57. Wharton SB, Wardle C, Ironside JW, et al (2003) Comparative genomic hybridization and pathological findings in atypical teratoid/rhabdoid tumour of the central nervous system. Neuropathol Appl Neurobiol 29:254–261

    Article  CAS  PubMed  Google Scholar 

  58. Rickert CH, Paulus W (2004) Chromosomal imbalances detected by comparative genomic hybridisation in atypical teratoid/rhabdoid tumours. Childs Nerv Syst 20:221–224

    Article  PubMed  Google Scholar 

  59. Burnett ME, White EC, Sih S, et al (1997) Chromosome arm 17p deletion analysis reveals molecular genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumors of the central nervous system. Cancer Genet Cytogenet 97:25–31

    Article  CAS  PubMed  Google Scholar 

  60. Eberhart CG, Chaudhry A, Daniel RW, et al (2005) Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus. BMC Cancer 5:19

    Article  PubMed  CAS  Google Scholar 

  61. Inda MM, Muñoz J, Coullin P, et al (2006) High promoter hypermethylation frequency of p14/ARF in supratentorial PNET but not in medulloblastoma. Histopathology (Oxf) 48:579–587

    Article  CAS  Google Scholar 

  62. Clifford SC, Lusher ME, Lindsey JC, et al (2006) Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblastomas associated with a favorable prognosis. Cell Cycle 5:2666–2670

    CAS  PubMed  Google Scholar 

  63. Yokota N, Nishizawa S, Ohta S, et al (2002) Role of Wnt pathway in medulloblastoma oncogenesis. Int J Cancer 101:198–201

    Article  CAS  PubMed  Google Scholar 

  64. Pietsch T, Waha A, Koch A, et al (1997) Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res 57:2085–2088

    CAS  PubMed  Google Scholar 

  65. Zurawel RH, Allen C, Chiappa S, et al (2000) Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosomes Cancer 27:44–51

    Article  CAS  PubMed  Google Scholar 

  66. Kraus JA, Oster C, Sörensen N, et al (2002) Human medulloblastomas lack point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene. Neuropathol Appl Neurobiol 28:136–141

    Article  CAS  PubMed  Google Scholar 

  67. Sévenet N, Lellouch-Tubiana A, Schofield D, et al (1999) Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. Hum Mol Genet 8: 2359–2368

    Article  PubMed  Google Scholar 

  68. Frese KK, Tuveson DA (2007) Maximizing mouse cancer models. Nat Rev Cancer 7:645–658

    Article  CAS  PubMed  Google Scholar 

  69. Fomchenko EI, Holland EC (2006) Mouse models of brain tumors and their applications in preclinical trials. Clin Cancer Res 12:5288–5297

    Article  CAS  PubMed  Google Scholar 

  70. Becher OJ, Holland EC (2006) Genetically engineered models have advantages over xenografts for preclinical studies. Cancer Res 66:3355–3358

    Article  CAS  PubMed  Google Scholar 

  71. Grisendi S, Pandolfi PP (2004) Germline modification strategies. In: Holland EC (ed) Mouse models of human cancers. Wiley, Hoboken, NJ, pp 43–65

    Google Scholar 

  72. Bates P, Young JA, Varmus HE (1993) A receptor for subgroup A Rous sarcoma virus is related to the low density lipoprotein receptor. Cell 74:1043–1051

    Article  CAS  PubMed  Google Scholar 

  73. Young JA, Bates P, Varmus HE (1993) Isolation of a chicken gene that confers susceptibility to infection by subgroup A avian leukosis and sarcoma viruses. J Virol 67:1811–1816

    CAS  PubMed  Google Scholar 

  74. Holland EC, Varmus HE (1998) Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice. Proc Natl Acad Sci U S A 95:1218–1223

    Article  CAS  PubMed  Google Scholar 

  75. Holland EC, Hively WP, DePinho RA, et al (1998) A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev 12:3675–3685

    Article  CAS  PubMed  Google Scholar 

  76. Goodrich LV, Milenkovi L, Higgins KM, et al (1997) Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277:1109–1113

    Article  CAS  PubMed  Google Scholar 

  77. Wetmore C, Eberhart DE, Curran T (2000) The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ-line mutation of patched. Cancer Res 60:2239–2246

    CAS  PubMed  Google Scholar 

  78. Zurawel RH, Allen C, Wechsler-Reya R, et al (2000) Evidence that haploinsufficiency of Ptch leads to medulloblastoma in mice. Genes Chromosomes Cancer 28:77–81

    Article  CAS  PubMed  Google Scholar 

  79. Hallahan AR, Pritchard JI, Hansen S, et al (2004) The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res 64:7794–7800

    Article  CAS  PubMed  Google Scholar 

  80. Weiner HL, Bakst R, Hurlbert MS, et al (2002) Induction of medulloblastomas in mice by sonic hedgehog, independent of Gli1. Cancer Res 62:6385–6389

    CAS  PubMed  Google Scholar 

  81. Rao G, Pedone CA, Coffin CM, et al (2003) c-Myc enhances sonic hedgehog-induced medulloblastoma formation from nestinexpressing neural progenitors in mice. Neoplasia 5:198–204

    CAS  PubMed  Google Scholar 

  82. Rao G, Pedone CA, Del Valle L, et al (2004) Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice. Oncogene 23:6156–6162

    Article  CAS  PubMed  Google Scholar 

  83. Browd SR, Kenney AM, Gottfried ON, et al (2006) N-myc can substitute for insulin-like growth factor signaling in a mouse model of sonic hedgehog-induced medulloblastoma. Cancer Res 66:2666–2672

    Article  CAS  PubMed  Google Scholar 

  84. McCall TD, Pedone CA, Fults DW (2007) Apoptosis suppression by somatic cell transfer of Bcl-2 promotes Sonic hedgehogdependent medulloblastoma formation in mice. Cancer Res 67: 5179–5185

    Article  CAS  PubMed  Google Scholar 

  85. Hahn H, Wojnowski L, Specht K, et al (2000) Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosarcoma. J Biol Chem 275:28 341–28 344

    CAS  Google Scholar 

  86. Briggs KJ, Corcoran-Schwartz IM, Zhang W, et al (2008) Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma. Genes Dev 22:770–785

    Article  CAS  PubMed  Google Scholar 

  87. Donehower LA, Harvey M, Slagle BL, et al (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature (Lond) 356:215–221

    Article  CAS  Google Scholar 

  88. Harvey M, McArthur MJ, Montgomery CA Jr, et al (1993) Genetic background alters the spectrum of tumors that develop in p53-deficient mice. FASEB J 7:938–943

    CAS  PubMed  Google Scholar 

  89. Jacks T, Remington L, Williams BO, et al (1994) Tumor spectrum analysis in p53-mutant mice. Curr Biol 4:1–7

    Article  CAS  PubMed  Google Scholar 

  90. Lee Y, McKinnon PJ (2002) DNA ligase IV suppresses medulloblastoma formation. Cancer Res 62:6395–6399

    CAS  PubMed  Google Scholar 

  91. Tong WM, Ohgaki H, Huang H, et al (2003) Null mutation of DNA strand break-binding molecule poly(ADP-ribose) polymerase causes medulloblastomas in p53(-/-) mice. Am J Pathol 162:343–352

    CAS  PubMed  Google Scholar 

  92. Wetmore C, Eberhart DE, Curran T (2001) Loss of p53 but not ARF accelerates medulloblastoma in mice heterozygous for patched. Cancer Res 61:513–516

    CAS  PubMed  Google Scholar 

  93. Lee Y, Kawagoe R, Sasai K, et al (2007) Loss of suppressor-offused function promotes tumorigenesis. Oncogene 26:6442–6447

    Article  CAS  PubMed  Google Scholar 

  94. Yan CT, Kaushal D, Murphy M, et al (2006) XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice. Proc Natl Acad Sci U S A 103:7378–7383

    Article  CAS  PubMed  Google Scholar 

  95. Frappart PO, Lee Y, Lamont J, et al (2007) BRCA2 is required for neurogenesis and suppression of medulloblastoma. EMBO J 26:2732–2742

    Article  CAS  PubMed  Google Scholar 

  96. Marino S, Vooijs M, van Der Gulden H, et al (2000) Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev 14:994–1004

    CAS  PubMed  Google Scholar 

  97. Uziel T, Zindy F, Xie S, et al (2005) The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation. Genes Dev 19:2656–2667

    Article  CAS  PubMed  Google Scholar 

  98. Theuring F, Götz W, Balling R, et al (1990) Tumorigenesis and eye abnormalities in transgenic mice expressing MSV-SV40 large T-antigen. Oncogene 5:225–232

    CAS  PubMed  Google Scholar 

  99. Marcus DM, Carpenter JL, O’Brien JM, et al (1991) Primitive neuroectodermal tumor of the midbrain in a murine model of retinoblastoma. Invest Ophthalmol Vis Sci 32:293–301

    CAS  PubMed  Google Scholar 

  100. al-Ubaidi MR, Font RL, Quiambao AB, et al (1992) Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. Cell Biol 119: 1681–1687

    Article  CAS  Google Scholar 

  101. Suri C, Fung BP, Tischler AS, et al (1993) Catecholaminergic cell lines from the brain and adrenal glands of tyrosine hydroxylase-SV40 T antigen transgenic mice. J Neurosci 13:1280–1291

    CAS  PubMed  Google Scholar 

  102. Krynska B, Otte J, Franks R, et al (1999) Human ubiquitous JCV(CY) T-antigen gene induces brain tumors in experimental animals. Oncogene 18:39–46

    Article  CAS  PubMed  Google Scholar 

  103. Sun Q, Wei X, Feng J, et al (2008) Involvement of insulin-like growth factor-insulin receptor signal pathway in the transgenic mouse model of medulloblastoma. Cancer Sci 99:234–240

    Article  CAS  PubMed  Google Scholar 

  104. Poulin DL, DeCaprio JA (2006) Is there a role for SV40 in human cancer? J Clin Oncol 24:4356–4365

    Article  CAS  PubMed  Google Scholar 

  105. Fults D, Pedone C, Dai C, et al (2002) MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo. Neoplasia 4:32–39

    Article  CAS  PubMed  Google Scholar 

  106. Momota H, Shih AH, Edgar MA, et al (2008) c-Myc and betacatenin cooperate with loss of p53 to generate multiple members of the primitive neuroectodermal tumor family in mice. Oncogene 27:4392–4401

    Article  CAS  PubMed  Google Scholar 

  107. Roberts CW, Galusha SA, McMenamin ME, et al (2000) Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc Natl Acad Sci U S A 97:13 796–13 800

    Article  CAS  Google Scholar 

  108. Klochendler-Yeivin A, Fiette L, Barra J, et al (2000) The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression. EMBO Rep 1: 500–506

    CAS  PubMed  Google Scholar 

  109. Guidi CJ, Sands AT, Zambrowicz BP, et al (2001) Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice. Mol Cell Biol 21:3598–3603

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurosurgery Division, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hiroyuki Momota

  2. Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Eric C. Holland

  3. Department of Surgery (Neurosurgery) and Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Eric C. Holland

Authors
  1. Hiroyuki Momota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric C. Holland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Momota.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Momota, H., Holland, E.C. Mouse models of CNS embryonal tumors. Brain Tumor Pathol 26, 43–50 (2009). https://doi.org/10.1007/s10014-009-0253-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-009-0253-0

Keywords

Search

Navigation