Lineage Relationships Connecting Germinal Regions to Brain Tumors

  • Nader Sanai
  • Arturo Alvarez-Buylla


Gliomas are a primary cancer of the brain and one of the most lethal cancers known to man. Historically, the neoplastic transformation of fully differentiated glia was widely assumed to be the only mechanism for gliomagenesis. Astrocytes and oligodendrocytes, once thought to be the sole dividing cells in the postnatal brain, were assumed to represent the cellular compartment most susceptible to transformation. More recently, however, this hypothesis has been challenged by the discovery of stem cell and progenitor populations residing in the postnatal brain, which may themselves serve as an origin of brain tumors. Phenotypic and behavioral similarities between gliomas and adult neural stem cells raise the possibility that stem or progenitor cells can give rise to gliomas. Possible candidate cells-of-origin include neuroepithelial cells, radial glia, astrocytic neural stem cells (‘B cells’), transient amplifying precursors (‘C cells’) of the adult subventricular zone (SVZ), or oligodendrocyte progenitor cells of the white matter. While a direct link has yet to be established between any one of these cell types and tumor formation, the different cell lineages arising from the ventricular and subventricular zone during development in the adult may offer clues in deciphering the origin of various tumor subtypes, including gliomas.


Neural Stem Cell Subventricular Zone Subcortical White Matter Radial Glia Neuroepithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Aboody KS, Brown A, Rainov NG, et al. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proceedings of the National Academy of Sciences of the United States of America 2000;97(23):12846–51.PubMedCrossRefGoogle Scholar
  2. Alvarez-Buylla A, Lim DA. For the long run: maintaining germinal niches in the adult brain. Neuron 2004;41(5):683–6.PubMedCrossRefGoogle Scholar
  3. Alvarez-Buylla A, Garcia-Verdugo JM, Tramontin AD. A unified hypothesis on the lineage of neural stem cells. Nature Reviews Neuroscience 2001;2(4):287–93.PubMedCrossRefGoogle Scholar
  4. Assanah M, Lochhead R, Ogden A, Bruce J, Goldman J, Canoll P. Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. Journal of Neuroscience 2006;26(25):6781–90.PubMedCrossRefGoogle Scholar
  5. Bachoo RM, Maher EA, Ligon KL, et al. Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 2002;1(3):269–77.PubMedCrossRefGoogle Scholar
  6. Bao S, Wu Q, Sathornsumetee S, et al. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Research 2006a;66(16):7843–8.PubMedCrossRefGoogle Scholar
  7. Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006b;444(7120):756–60.PubMedCrossRefGoogle Scholar
  8. Bar EE, Chaudhry A, Lin A, et al. Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma. Stem Cells 2007;25(10):2524–33.PubMedCrossRefGoogle Scholar
  9. Becker AJ, Klein H, Baden T, et al. Mutational and expression analysis of the reelin pathway components CDK5 and doublecortin in gangliogliomas. Acta Neuropathologica 2002;104(4):403–8.PubMedGoogle Scholar
  10. Bedard A, Parent A. Evidence of newly generated neurons in the human olfactory bulb. Brain Research. Developmental Brain Research 2004;151(1–2):159–68.PubMedCrossRefGoogle Scholar
  11. Campisi J. Aging and cancer cell biology, 2007. Aging Cell 2007;6(3):261–3.PubMedCrossRefGoogle Scholar
  12. Capela A, Temple S. LeX is expressed by principle progenitor cells in the embryonic nervous system, is secreted into their environment and binds Wnt-1. Developmental Biology 2006;291(2):300–13.PubMedCrossRefGoogle Scholar
  13. Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Current Biology 2007;17(2):165–72.PubMedCrossRefGoogle Scholar
  14. Curtis MA, Kam M, Nannmark U, et al. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science 2007;315(5816):1243–9.PubMedCrossRefGoogle Scholar
  15. Dahmane N, Sanchez P, Gitton Y, et al. The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 2001;128(24):5201–12.PubMedGoogle Scholar
  16. Daou MC, Smith TW, Litofsky NS, Hsieh CC, Ross AH. Doublecortin is preferentially expressed in invasive human brain tumors. Acta Neuropathologica 2005;110(5):472–80.PubMedCrossRefGoogle Scholar
  17. Doetsch F, Alvarez-Buylla A. Network of tangential pathways for neuronal migration in adult mammalian brain. Proceedings of the National Academy of Sciences of the United States of America 1996;93(25):14895–900.Google Scholar
  18. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. Journal of Neuroscience 1997;17(13):5046–61.PubMedGoogle Scholar
  19. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999;97(6):703–16.PubMedCrossRefGoogle Scholar
  20. Doetsch F, Petreanu L, Caille I, Garcia-Verdugo JM, Alvarez-Buylla A. EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 2002a;36(6):1021–34.PubMedCrossRefGoogle Scholar
  21. Doetsch F, Verdugo JM, Caille I, Alvarez-Buylla A, Chao MV, Casaccia-Bonnefil P. Lack of the cell-cycle inhibitor p27Kip1 results in selective increase of transit-amplifying cells for adult neurogenesis. Journal of Neuroscience 2002b;22(6):2255–64.PubMedGoogle Scholar
  22. Feldkamp MM, Lau N, Guha A. Signal transduction pathways and their relevance in human astrocytomas. Journal of Neuro-oncology 1997;35(3):223–48.PubMedCrossRefGoogle Scholar
  23. Fischer I, Gagner JP, Law M, Newcomb EW, Zagzag D. Angiogenesis in gliomas: biology and molecular pathophysiology. Brain Pathology 2005;15(4):297–310.PubMedCrossRefGoogle Scholar
  24. Galli R, Binda E, Orfanelli U, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Research 2004;64(19):7011–21.PubMedCrossRefGoogle Scholar
  25. Garcia-Verdugo JM, Doetsch F, Wichterle H, Lim DA, Alvarez-Buylla A. Architecture and cell types of the adult subventricular zone: in search of the stem cells. Journal of Neurobiology 1998;36(2):234–48.PubMedCrossRefGoogle Scholar
  26. Gilbertson RJ, Rich JN. Making a tumour's bed: glioblastoma stem cells and the vascular niche. Nature Reviews 2007;7(10):733–6.PubMedCrossRefGoogle Scholar
  27. Gil-Perotin S, Marin-Husstege M, Li J, et al. Loss of p53 induces changes in the behavior of subventricular zone cells: implication for the genesis of glial tumors. Journal of Neuroscience 2006;26(4):1107–16.PubMedCrossRefGoogle Scholar
  28. Hambardzumyan D, Squatrito M, Holland EC. Radiation resistance and stem-like cells in brain tumors. Cancer Cell 2006;10(6):454–6.PubMedCrossRefGoogle Scholar
  29. Hesselager G, Uhrbom L, Westermark B, Nister M. Complementary effects of platelet-derived growth factor autocrine stimulation and p53 or Ink4a-Arf deletion in a mouse glioma model. Cancer Research 2003;63(15):4305–9.PubMedGoogle Scholar
  30. Hopewell JW. The subependymal plate and the genesis of gliomas. The Journal of Pathology 1975;117(2):101–3.PubMedCrossRefGoogle Scholar
  31. Humphrey TJ. The development of the olfactory and accessory olfactory formation in human embryos and fetuses. Journal of Comparative Neurology 1940;73:431–68.CrossRefGoogle Scholar
  32. Ivanchuk SM, Mondal S, Dirks PB, Rutka JT. The INK4A/ARF locus: role in cell cycle control and apoptosis and implications for glioma growth. Journal of Neuro-oncology 2001;51(3):219–29.PubMedCrossRefGoogle Scholar
  33. Jackson EL, Garcia-Verdugo JM, Gil-Perotin S, et al. PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 2006;51(2):187–99.PubMedCrossRefGoogle Scholar
  34. Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT. Angiogenesis in brain tumours. Nature Reviews Neuroscience 2007;8(8):610–22.PubMedCrossRefGoogle Scholar
  35. Jang T, Litofsky NS, Smith TW, Ross AH, Recht LD. Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis. Neurobiology of Disease 2004;15(3):544–52.PubMedCrossRefGoogle Scholar
  36. Kakita A, Goldman JE. Patterns and dynamics of SVZ cell migration in the postnatal forebrain: monitoring living progenitors in slice preparations. Neuron 1999;23(3):461–72.PubMedCrossRefGoogle Scholar
  37. Kakita A, Zerlin M, Takahashi H, Goldman JE. Some glial progenitors in the neonatal subventricular zone migrate through the corpus callosum to the contralateral cerebral hemisphere. The Journal of Comparative Neurology 2003;458(4):381–8.PubMedCrossRefGoogle Scholar
  38. Katayama K, Ueno M, Yamauchi H, Nagata T, Nakayama H, Doi K. Ethylnitrosourea induces neural progenitor cell apoptosis after S-phase accumulation in a p53-dependent manner. Neurobiology of Disease 2005;18(1):218–25.PubMedCrossRefGoogle Scholar
  39. Kenney AM, Cole MD, Rowitch DH. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 2003;130(1):15–28.PubMedCrossRefGoogle Scholar
  40. Kim JY, Nelson AL, Algon SA, et al. Medulloblastoma tumorigenesis diverges from cerebellar granule cell differentiation in patched heterozygous mice. Developmental Biology 2003;263(1):50–66.PubMedCrossRefGoogle Scholar
  41. Knizetova P, Darling JL, Bartek J. Vascular endothelial growth factor in astroglioma stem cell biology and response to therapy. Journal of Cellular and Molecular Medicine 2008;12(1):111–25.PubMedCrossRefGoogle Scholar
  42. Kornack DR, Rakic P. The generation, migration, and differentiation of olfactory neurons in the adult primate brain. Proceedings of the National Academy of Sciences of the United States of America 2001;98(8):4752–7.Google Scholar
  43. Kriegstein A, Noctor S, Martinez-Cerdeno V. Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nature Reviews Neuroscience 2006;7(11):883–90.PubMedCrossRefGoogle Scholar
  44. Kuan CT, Wikstrand CJ, Bigner DD. EGF mutant receptor vIII as a molecular target in cancer therapy. Endocrine-Related Cancer 2001;8(2):83–96.PubMedCrossRefGoogle Scholar
  45. Lachyankar MB, Sultana N, Schonhoff CM, et al. A role for nuclear PTEN in neuronal differentiation. Journal of Neuroscience 2000;20(4):1404–13.PubMedGoogle Scholar
  46. Lantos PL. The role of the subependymal plate in the origin of gliomas induced by ethylnitrosourea in the rat brain. Experientia 1977;33(4):521–2.PubMedCrossRefGoogle Scholar
  47. Lantos PL, Cox DJ. The origin of experimental brain tumours: a sequential study. Experientia 1976;32(11):1467–8.PubMedCrossRefGoogle Scholar
  48. Lantos PL, Pilkington GJ. The development of experimental brain tumours. A sequential light and electron microscope study of the subependymal plate. I. Early lesions (abnormal cell clusters). Acta Neuropathologica 1979;45(3):167–75.PubMedCrossRefGoogle Scholar
  49. Lassman AB. Molecular biology of gliomas. Current Neurology and Neuroscience Reports 2004;4(3):228–33.PubMedCrossRefGoogle Scholar
  50. Li L, Liu F, Ross AH. PTEN regulation of neural development and CNS stem cells. Journal of Cellular Biochemistry 2003;88(1):24–8.PubMedCrossRefGoogle Scholar
  51. Lim DA, Cha S, Mayo MC, et al. Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro-oncology 2007;9(4):424–9.PubMedCrossRefGoogle Scholar
  52. Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science 1994;264(5162):1145–8.PubMedCrossRefGoogle Scholar
  53. Lois C, Garcia-Verdugo JM, Alvarez-Buylla A. Chain migration of neuronal precursors. Science 1996;271(5251):978–81.PubMedCrossRefGoogle Scholar
  54. Luskin MB. Neuroblasts of the postnatal mammalian forebrain: their phenotype and fate. Journal of Neurobiology 1998;36(2):221–33.PubMedCrossRefGoogle Scholar
  55. Menn B, Garcia-Verdugo JM, Yaschine C, Gonzalez-Perez O, Rowitch D, Alvarez-Buylla A. Origin of oligodendrocytes in the subventricular zone of the adult brain. Journal of Neuroscience 2006;26(30):7907–18.PubMedCrossRefGoogle Scholar
  56. Mercier F, Kitasako JT, Hatton GI. Anatomy of the brain neurogenic zones revisited: fractones and the fibroblast/macrophage network. The Journal of Comparative Neurology 2002;451(2):170–88.PubMedCrossRefGoogle Scholar
  57. Merkle FT, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A. Radial glia give rise to adult neural stem cells in the subventricular zone. Proceedings of the National Academy of Sciences of the United States of America 2004;101(50):17528–32.Google Scholar
  58. Merkle FT, Mirzadeh Z, Alvarez-Buylla A. Mosaic organization of neural stem cells in the adult brain. Science 2007;317(5836):381–4.PubMedCrossRefGoogle Scholar
  59. Mirzadeh Z, Merkle FT, Soriano-Navarro M, et al. Neural stem cells confer unique pinwheel architecture to the ventricular surface of neurogenic regions of the adult brain. Cell Stem Cell. 2008 Sep 11;3(3):265–78.Google Scholar
  60. Molofsky AV, Slutsky SG, Joseph NM, et al. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 2006;443(7110):448–52.PubMedCrossRefGoogle Scholar
  61. Mueller A, Abolmaali ND, Hakimi AR, et al. Olfactory bulb volumes in patients with idiopathic Parkinson's disease a pilot study. Journal of Neural Transmission 2005;112(10):1363–70.PubMedCrossRefGoogle Scholar
  62. Muller F, O'Rahilly R. The human brain at stage 17, including the appearance of the future olfactory bulb and the first amygdaloid nuclei. Anatomy and Embryology (Berl) 1989;180(4):353–69.CrossRefGoogle Scholar
  63. Mullor JL, Sanchez P, Altaba AR. Pathways and consequences: Hedgehog signaling in human disease. Trends in Cell Biology 2002;12(12):562–9.PubMedCrossRefGoogle Scholar
  64. Nacher J, Crespo C, McEwen BS. Doublecortin expression in the adult rat telencephalon. The European Journal of Neuroscience 2001;14(4):629–44.PubMedCrossRefGoogle Scholar
  65. Nakano I, Saigusa K, Kornblum HI. BMPing off glioma stem cells. Cancer Cell 2008;13(1):3–4.PubMedCrossRefGoogle Scholar
  66. Nakashima T, Kimmelman CP, Snow JB, Jr. Immunohistopathology of human olfactory epithelium, nerve and bulb. Laryngoscope 1985;95(4):391–6.PubMedCrossRefGoogle Scholar
  67. Noble M, Wren D, Wolswijk G. The O-2A(adult) progenitor cell: a glial stem cell of the adult central nervous system. Seminars in Cell Biology 1992;3(6):413–22.PubMedCrossRefGoogle Scholar
  68. Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR. Neurons derived from radial glial cells establish radial units in neocortex. Nature 2001;409(6821):714–20.PubMedCrossRefGoogle Scholar
  69. Nunes MC, Roy NS, Keyoung HM, et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nature Medicine 2003;9(4):439–47.PubMedCrossRefGoogle Scholar
  70. Palma V, Lim DA, Dahmane N, et al. Sonic hedgehog controls stem cell behavior in the postnatal and adult brain. Development 2005;132(2):335–44.PubMedCrossRefGoogle Scholar
  71. Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis. The Journal of Comparative Neurology 2000;425(4):479–94.PubMedCrossRefGoogle Scholar
  72. Panchision DM, Pickel JM, Studer L, et al. Sequential actions of BMP receptors control neural precursor cell production and fate. Genes & Development 2001;15(16):2094–110.CrossRefGoogle Scholar
  73. Pfenninger CV, Roschupkina T, Hertwig F, et al. CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells. Cancer Research 2007;67(12):5727–36.PubMedCrossRefGoogle Scholar
  74. Pilkington GJ, Lantos PL. The development of experimental brain tumours a sequential light and electron microscope study of the subependymal plate. II. Microtumours. Acta Neuropathologica 1979;45(3):177–85.Google Scholar
  75. Quinones-Hinojosa A, Sanai N, Soriano-Navarro M, et al. Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. The Journal of Comparative Neurology 2006;494(3):415–34.PubMedCrossRefGoogle Scholar
  76. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992;255(5052):1707–10.PubMedCrossRefGoogle Scholar
  77. Roy NS, Wang S, Harrison-Restelli C, et al. Identification, isolation, and promoter-defined separation of mitotic oligodendrocyte progenitor cells from the adult human subcortical white matter. Journal of Neuroscience 1999;19(22):9986–95.PubMedGoogle Scholar
  78. Rubin JB, Rowitch DH. Medulloblastoma: a problem of developmental biology. Cancer Cell 2002;2(1):7–8.PubMedCrossRefGoogle Scholar
  79. Sanai N, Tramontin AD, Quinones-Hinojosa A, et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 2004;427(6976):740–4.PubMedCrossRefGoogle Scholar
  80. Sanai N, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A. Comment on “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science 2007;318(5849):393; author reply.PubMedCrossRefGoogle Scholar
  81. Santra M, Liu XS, Santra S, et al. Ectopic expression of doublecortin protects adult rat progenitor cells and human glioma cells from severe oxygen and glucose deprivation. Neuroscience 2006;142(3):739–52.PubMedCrossRefGoogle Scholar
  82. Savarese TM, Jang T, Low HP, et al. Isolation of immortalized, INK4a/ARF-deficient cells from the subventricular zone after in utero N-ethyl-N-nitrosourea exposure. Journal of Neurosurgery 2005;102(1):98–108.PubMedCrossRefGoogle Scholar
  83. Schulenburg A, Ulrich-Pur H, Thurnher D, et al. Neoplastic stem cells: a novel therapeutic target in clinical oncology. Cancer 2006;107(10):2512–20.PubMedCrossRefGoogle Scholar
  84. Shih AH, Holland EC. Platelet-derived growth factor (PDGF) and glial tumorigenesis. Cancer Letters 2006;232(2):139–47.PubMedCrossRefGoogle Scholar
  85. Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavanee W, Vogelstein B. Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature 1992;355(6363):846–7.PubMedCrossRefGoogle Scholar
  86. Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Research 2003;63(18):5821–8.PubMedGoogle Scholar
  87. Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature 2004a;432(7015):396–401.PubMedCrossRefGoogle Scholar
  88. Singh SK, Clarke ID, Hide T, Dirks PB. Cancer stem cells in nervous system tumors. Oncogene 2004b;23(43):7267–73.PubMedCrossRefGoogle Scholar
  89. Spassky N, Merkle FT, Flames N, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A. Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. Journal of Neuroscience 2005;25(1):10–8.PubMedCrossRefGoogle Scholar
  90. Tang Y, Shah K, Messerli SM, Snyder E, Breakefield X, Weissleder R. In vivo tracking of neural progenitor cell migration to glioblastomas. Human Gene Therapy 2003;14(13):1247–54.PubMedCrossRefGoogle Scholar
  91. Tavazoie M, Van der Veken L, Silva-Vargas V, et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 2008 Sep 11;3(3):279–88.Google Scholar
  92. Varga AC, Wrana JL. The disparate role of BMP in stem cell biology. Oncogene 2005;24(37):5713–21.PubMedCrossRefGoogle Scholar
  93. Vick NA, Lin MJ, Bigner DD. The role of the subependymal plate in glial tumorigenesis. Acta Neuropathologica 1977;40(1):63–71.PubMedCrossRefGoogle Scholar
  94. Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 1999;22(1):103–14.PubMedCrossRefGoogle Scholar
  95. Wechsler-Reya R, Scott MP. The developmental biology of brain tumors. Annual Review of Neuroscience 2001;24:385–428.PubMedCrossRefGoogle Scholar
  96. Wiese C, Rolletschek A, Kania G, et al. Nestin expression—a property of multi-lineage progenitor cells? Cellular and Molecular Life Sciences 2004;61(19–20):2510–22.PubMedCrossRefGoogle Scholar
  97. Wolswijk G, Noble M. Cooperation between PDGF and FGF converts slowly dividing O-2Aadult progenitor cells to rapidly dividing cells with characteristics of O-2Aperinatal progenitor cells. The Journal of Cell Biology 1992;118(4):889–900.PubMedCrossRefGoogle Scholar
  98. Wolswijk G, Riddle PN, Noble M. Platelet-derived growth factor is mitogenic for O-2Aadult progenitor cells. Glia 1991;4(5):495–503.PubMedCrossRefGoogle Scholar
  99. Yang XH, Wu QL, Yu XB, et al. Nestin expression in different tumours and its relevance to malignant grade. Journal of Clinical Pathology 2008;61(4):467–73.PubMedCrossRefGoogle Scholar
  100. Zhu Y, Guignard F, Zhao D, et al. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 2005;8(2):119–30.PubMedCrossRefGoogle Scholar
  101. Zolota V, Tsamandas AC, Aroukatos P, et al. Expression of cell cycle inhibitors p21, p27, p14 and p16 in gliomas. Correlation with classic prognostic factors and patients' outcome. Neuropathology 2008;28(1):35–42.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Institute for Regeneration Medicine and Department of Neurological SurgeryUniversity of California at San FranciscoSan FranciscoUSA
  2. 2.Neurosurgery Research, University of California San FranciscoSan FranciscoUSA

Personalised recommendations