1932

Abstract

After more than a decade of genomic studies in medulloblastoma, the time has come to capitalize on the knowledge gained and use it to directly improve patient care. Although metastatic and relapsed disease remain poorly understood, much has changed in how we define medulloblastoma, and it has become evident that with conventional therapies, specific groups of patients are currently under- or overtreated. In this review, we summarize the latest insights into medulloblastoma biology, focusing on how genomics is affecting patient stratification, informing preclinical studies of targeted therapies, and shaping the new generation of clinical trials.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-091416-035434
2017-08-31
2024-06-24
Loading full text...

Full text loading...

/deliver/fulltext/genom/18/1/annurev-genom-091416-035434.html?itemId=/content/journals/10.1146/annurev-genom-091416-035434&mimeType=html&fmt=ahah

Literature Cited

  1. Abraham H, Tornoczky T, Kosztolanyi G, Seress L. 1.  2001. Cell formation in the cortical layers of the developing human cerebellum. Int. J. Dev. Neurosci. 19:53–62 [Google Scholar]
  2. Albright AL, Wisoff JH, Zeltzer PM, Boyett JM, Rorke LB, Stanley P. 2.  1996. Effects of medulloblastoma resections on outcome in children: a report from the Children's Cancer Group. Neurosurgery 38:265–71 [Google Scholar]
  3. Alimova I, Venkataraman S, Harris P, Marquez VE, Northcott PA. 3.  et al. 2012. Targeting the enhancer of zeste homologue 2 in medulloblastoma. Int. J. Cancer 131:1800–9 [Google Scholar]
  4. Beauchamp EM, Ringer L, Bulut G, Sajwan KP, Hall MD. 4.  et al. 2011. Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway. J. Clin. Investig. 121:148–60 [Google Scholar]
  5. Chang CH, Housepian EM, Herbert C Jr. 5.  1969. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93:1351–59 [Google Scholar]
  6. Chizhikov VV, Lindgren AG, Mishima Y, Roberts RW, Aldinger KA. 6.  et al. 2010. Lmx1a regulates fates and location of cells originating from the cerebellar rhombic lip and telencephalic cortical hem. PNAS 107:10725–30 [Google Scholar]
  7. Cho Y-J, Tsherniak A, Tamayo P, Santagata S, Ligon A. 7.  et al. 2011. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J. Clin. Oncol. 29:1424–30 [Google Scholar]
  8. Clifford SC, Lannering B, Schwalbe EC, Hicks D, Toole KO. 8.  et al. 2015. Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: results from the multi-center HIT-SIOP-PNET4 clinical trial. Oncotarget 6:38827–39 [Google Scholar]
  9. Cohen BH, Geyer JR, Miller DC, Curran JG, Zhou T. 9.  et al. 2015. Pilot study of intensive chemotherapy with peripheral hematopoietic cell support for children less than 3 years of age with malignant brain tumors, the CCG-99703 phase I/II study. A report from the Children's Oncology Group. Pediatr. Neurol. 53:31–46 [Google Scholar]
  10. Cooper MK, Wassif CA, Krakowiak PA, Taipale J, Gong R. 10.  et al. 2003. A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis. Nat. Genet. 33:508–13 [Google Scholar]
  11. Dubuc AM, Mack S, Unterberger A, Northcott PA, Taylor MD. 11.  2012. The epigenetics of brain tumors. Methods Mol. Biol. 863:139–53 [Google Scholar]
  12. Dubuc AM, Remke M, Korshunov A, Northcott PA, Zhan SH. 12.  et al. 2013. Aberrant patterns of H3K4 and H3K27 histone lysine methylation occur across subgroups in medulloblastoma. Acta Neuropathol 125:373–84 [Google Scholar]
  13. Dunkel IJ, Boyett JM, Yates A, Rosenblum M, Garvin JH Jr.. 13.  et al. (Children's Cancer Group) 1998. High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. J. Clin. Oncol. 16:222–28 [Google Scholar]
  14. Ellison DW, Onilude OE, Lindsey JC, Lusher ME, Weston CL. 14.  et al. 2005. β-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee. J. Clin. Oncol. 23:7951–57 [Google Scholar]
  15. Fouladi M, Blaney SM, Poussaint TY, Freeman BB III, McLendon R. 15.  et al. 2006. Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors: a pediatric brain tumor consortium study. Cancer 107:2291–97 [Google Scholar]
  16. Gadson DR, Emery JL. 16.  1976. Some quantitative morphological aspects of post-natal human cerebellar growth. J. Neurol. Sci. 29:137–48 [Google Scholar]
  17. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE. 17.  et al. 2006. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol 7:813–20 [Google Scholar]
  18. Gajjar A, Stewart CF, Ellison DW, Kaste SC, Kun LE. 18.  et al. 2013. Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a Pediatric Brain Tumor Consortium study. Clin. Cancer Res. 19:6305–12 [Google Scholar]
  19. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS. 19.  et al. 2010. Subtypes of medulloblastoma have distinct developmental origins. Nature 468:1095–99 [Google Scholar]
  20. Gilbertson RJ, Ellison DW. 20.  2008. The origins of medulloblastoma subtypes. Annu. Rev. Pathol. 3:341–65 [Google Scholar]
  21. Gottardo NG, Hansford JR, McGlade JP, Alvaro F, Ashley DM. 21.  et al. 2014. Medulloblastoma Down Under 2013: a report from the third annual meeting of the International Medulloblastoma Working Group. Acta Neuropathol 127:189–201 [Google Scholar]
  22. Gururangan S, Krauser J, Watral MA, Driscoll T, Larrier N. 22.  et al. 2008. Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma. Neuro-Oncology 10:745–51 [Google Scholar]
  23. Haldipur P, Bharti U, Govindan S, Sarkar C, Iyengar S. 23.  et al. 2012. Expression of Sonic hedgehog during cell proliferation in the human cerebellum. Stem Cells Dev 21:1059–68 [Google Scholar]
  24. Hill RM, Kuijper S, Lindsey JC, Petrie K, Schwalbe EC. 24.  et al. 2015. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. Cancer Cell 27:72–84 [Google Scholar]
  25. Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M. 25.  et al. 2005. Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron 47:201–13 [Google Scholar]
  26. Hovestadt V, Jones DT, Picelli S, Wang W, Kool M. 26.  et al. 2014. Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature 510:537–41 [Google Scholar]
  27. Hu J, Liu YF, Wu CF, Xu F, Shen ZX. 27.  et al. 2009. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. PNAS 106:3342–47 [Google Scholar]
  28. Jones DT, Jager N, Kool M, Zichner T, Hutter B. 28.  et al. 2012. Dissecting the genomic complexity underlying medulloblastoma. Nature 488:100–5 [Google Scholar]
  29. Jones DT, Northcott PA, Kool M, Pfister SM. 29.  2013. The role of chromatin remodeling in medulloblastoma. Brain Pathol 23:193–99 [Google Scholar]
  30. Jones PA, Issa JP, Baylin S. 30.  2016. Targeting the cancer epigenome for therapy. Nat. Rev. Genet. 17:630–41 [Google Scholar]
  31. Kawauchi D, Robinson G, Uziel T, Gibson P, Rehg J. 31.  et al. 2012. A mouse model of the most aggressive subgroup of human medulloblastoma. Cancer Cell 21:168–80 [Google Scholar]
  32. Kim J, Lee JJ, Kim J, Gardner D, Beachy PA. 32.  2010. Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector. PNAS 107:13432–37 [Google Scholar]
  33. Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ. 33.  et al. 2014. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 25:393–405 [Google Scholar]
  34. Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M. 34.  et al. 2012. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathol 123:473–84 [Google Scholar]
  35. Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A. 35.  et al. 2008. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLOS ONE 3:e3088 [Google Scholar]
  36. Kortmann RD, Kuhl J, Timmermann B, Mittler U, Urban C. 36.  et al. 2000. Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91. Int. J. Radiat. Oncol. Biol. Phys. 46:269–79 [Google Scholar]
  37. Lafay-Cousin L, Smith A, Chi SN, Wells E, Madden J. 37.  et al. 2016. Clinical, pathological, and molecular characterization of infant medulloblastomas treated with sequential high-dose chemotherapy. Pediatr. Blood Cancer 63:1527–34 [Google Scholar]
  38. Lastowska M, Al-Afghani H, Al-Balool HH, Sheth H, Mercer E. 38.  et al. 2013. Identification of a neuronal transcription factor network involved in medulloblastoma development. Acta Neuropathol. Commun. 1:35 [Google Scholar]
  39. Lin CY, Erkek S, Tong Y, Yin L, Federation AJ. 39.  et al. 2016. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature 530:57–62 [Google Scholar]
  40. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D. 40.  et al. 2016. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–20 [Google Scholar]
  41. Marzban H, Del Bigio MR, Alizadeh J, Ghavami S, Zachariah RM, Rastegar M. 41.  2014. Cellular commitment in the developing cerebellum. Front. Cell Neurosci. 8:450 [Google Scholar]
  42. Metcalfe C, de Sauvage FJ. 42.  2011. Hedgehog fights back: mechanisms of acquired resistance against Smoothened antagonists. Cancer Res 71:5057–61 [Google Scholar]
  43. Morfouace M, Shelat A, Jacus M, Freeman BB III, Turner D. 43.  et al. 2014. Pemetrexed and gemcitabine as combination therapy for the treatment of Group 3 medulloblastoma. Cancer Cell 25:516–29 [Google Scholar]
  44. Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang X. 44.  et al. 2016. Divergent clonal selection dominates medulloblastoma at recurrence. Nature 529:351–57 [Google Scholar]
  45. Moxon-Emre I, Taylor MD, Bouffet E, Hardy K, Campen CJ. 45.  et al. 2016. Intellectual outcome in molecular subgroups of medulloblastoma. J. Clin. Oncol. 34:4161–70 [Google Scholar]
  46. Müller F, O'Rahilly R. 46.  1989. The human brain at stage 16, including the initial evagination of the neurohypophysis. Anat. Embryol. 179:551–69 [Google Scholar]
  47. Müller F, O'Rahilly R. 47.  1990. The human brain at stages 21–23, with particular reference to the cerebral cortical plate and to the development of the cerebellum. Anat. Embryol. 182:375–400 [Google Scholar]
  48. Mumert M, Dubuc A, Wu X, Northcott PA, Chin SS. 48.  et al. 2012. Functional genomics identifies drivers of medulloblastoma dissemination. Cancer Res 72:4944–53 [Google Scholar]
  49. Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ. 49.  et al. 2012. Medulloblastomics: the end of the beginning. Nat. Rev. Cancer 12:818–34 [Google Scholar]
  50. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG. 50.  et al. 2011. Medulloblastoma comprises four distinct molecular variants. J. Clin. Oncol. 29:1408–14 [Google Scholar]
  51. Northcott PA, Lee C, Zichner T, Stutz AM, Erkek S. 51.  et al. 2014. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428–34 [Google Scholar]
  52. Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS. 52.  et al. 2012. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 488:49–56 [Google Scholar]
  53. Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R. 53.  et al. 2015. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-Oncology 17:Suppl. 4iv1–62 [Google Scholar]
  54. Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC. 54.  et al. 2006. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J. Clin. Oncol. 24:4202–8 [Google Scholar]
  55. Parsons DW, Li M, Zhang X, Jones S, Leary RJ. 55.  et al. 2011. The genetic landscape of the childhood cancer medulloblastoma. Science 331:435–39 [Google Scholar]
  56. Pei Y, Liu KW, Wang J, Garancher A, Tao R. 56.  et al. 2016. HDAC and PI3K antagonists cooperate to inhibit growth of MYC-driven medulloblastoma. Cancer Cell 29:311–23 [Google Scholar]
  57. Pei Y, Moore CE, Wang J, Tewari AK, Eroshkin A. 57.  et al. 2012. An animal model of MYC-driven medulloblastoma. Cancer Cell 21:155–67 [Google Scholar]
  58. Perreault S, Ramaswamy V, Achrol AS, Chao K, Liu TT. 58.  et al. 2014. MRI surrogates for molecular subgroups of medulloblastoma. Am. J. Neuroradiol. 35:1263–69 [Google Scholar]
  59. Pfaff E, Remke M, Sturm D, Benner A, Witt H. 59.  et al. 2010. TP53 mutation is frequently associated with CTNNB1 mutation or MYCN amplification and is compatible with long-term survival in medulloblastoma. J. Clin. Oncol 28:5188–96 [Google Scholar]
  60. Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH. 60.  et al. 2006. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–73 [Google Scholar]
  61. Phoenix TN, Patmore DM, Boop S, Boulos N, Jacus MO. 61.  et al. 2016. Medulloblastoma genotype dictates blood brain barrier phenotype. Cancer Cell 29:508–22 [Google Scholar]
  62. Pietsch T, Schmidt R, Remke M, Korshunov A, Hovestadt V. 62.  et al. 2014. Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol 128:137–49 [Google Scholar]
  63. Pizer B, Donachie PH, Robinson K, Taylor RE, Michalski A. 63.  et al. 2011. Treatment of recurrent central nervous system primitive neuroectodermal tumours in children and adolescents: results of a Children's Cancer and Leukaemia Group study. Eur. J. Cancer 47:1389–97 [Google Scholar]
  64. Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M. 64.  et al. 2002. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–42 [Google Scholar]
  65. Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D. 65.  et al. 2012. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488:106–10 [Google Scholar]
  66. Rakic P, Sidman RL. 66.  1970. Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J. Comp. Neurol. 139:473–500 [Google Scholar]
  67. Ramaswamy V, Remke M, Adamski J, Bartels U, Tabori U. 67.  et al. 2016. Medulloblastoma subgroup-specific outcomes in irradiated children: Who are the true high-risk patients?. Neuro-Oncology 18:291–97 [Google Scholar]
  68. Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC. 68.  et al. 2016. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol 131:821–31 [Google Scholar]
  69. Ramaswamy V, Remke M, Bouffet E, Faria CC, Perreault S. 69.  et al. 2013. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 14:1200–7 [Google Scholar]
  70. Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T. 70.  et al. 2012. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148:59–71 [Google Scholar]
  71. Remke M, Ramaswamy V, Peacock J, Shih DJ, Koelsche C. 71.  et al. 2013. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma. Acta Neuropathol 126:917–29 [Google Scholar]
  72. Robinson GW, Orr BA, Wu G, Gururangan S, Lin T. 72.  et al. 2015. Vismodegib exerts targeted efficacy against recurrent sonic hedgehog-subgroup medulloblastoma: results from phase II Pediatric Brain Tumor Consortium studies PBTC-025B and PBTC-032. J. Clin. Oncol. 33:2646–54 [Google Scholar]
  73. Robinson GW, Parker M, Kranenburg TA, Lu C, Chen X. 73.  et al. 2012. Novel mutations target distinct subgroups of medulloblastoma. Nature 488:43–48 [Google Scholar]
  74. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA. 74.  et al. 2009. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N. Engl. J. Med. 361:1173–78 [Google Scholar]
  75. Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M. 75.  et al. 2005. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N. Engl. J. Med. 352:978–86 [Google Scholar]
  76. Salaroli R, Ronchi A, Buttarelli FR, Cortesi F, Marchese V. 76.  et al. 2015. Wnt activation affects proliferation, invasiveness and radiosensitivity in medulloblastoma. J. Neurooncol. 121:119–27 [Google Scholar]
  77. Sanders RP, Onar A, Boyett JM, Broniscer A, Morris EB. 77.  et al. 2008. M1 medulloblastoma: high risk at any age. J. Neurooncol. 90:351–55 [Google Scholar]
  78. Schüller U, Heine VM, Mao J, Kho AT, Dillon AK. 78.  et al. 2008. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell 14:123–34 [Google Scholar]
  79. Shih C-S, Hale GA, Gronewold L, Tong X, Laningham FH. 79.  et al. 2008. High-dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors. Cancer 112:1345–53 [Google Scholar]
  80. Shih DJ, Northcott PA, Remke M, Korshunov A, Ramaswamy V. 80.  et al. 2014. Cytogenetic prognostication within medulloblastoma subgroups. J. Clin. Oncol. 32:886–96 [Google Scholar]
  81. Skowron P, Ramaswamy V, Taylor MD. 81.  2015. Genetic and molecular alterations across medulloblastoma subgroups. J. Mol. Med. 93:1075–84 [Google Scholar]
  82. Sottoriva A, Spiteri I, Piccirillo SG, Touloumis A, Collins VP. 82.  et al. 2013. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. PNAS 110:4009–14 [Google Scholar]
  83. Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG. 83.  et al. 2002. Mutations in SUFU predispose to medulloblastoma. Nat. Genet. 31:306–10 [Google Scholar]
  84. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ. 84.  et al. 2012. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123:465–72 [Google Scholar]
  85. Taylor RE, Bailey CC, Robinson KJ, Weston CL, Walker DA. 85.  et al. 2005. Outcome for patients with metastatic (M2–3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur. J. Cancer 41:727–34 [Google Scholar]
  86. Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B. 86.  et al. 2016. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol 17:484–95 [Google Scholar]
  87. von Bueren AO, Kortmann RD, von Hoff K, Friedrich C, Mynarek M. 87.  et al. 2016. Treatment of children and adolescents with metastatic medulloblastoma and prognostic relevance of clinical and biologic parameters. J. Clin. Oncol. 34:4151–60 [Google Scholar]
  88. Wang X, Dubuc AM, Ramaswamy V, Mack S, Gendoo DM. 88.  et al. 2015. Medulloblastoma subgroups remain stable across primary and metastatic compartments. Acta Neuropathol 129:449–57 [Google Scholar]
  89. Wechsler-Reya RJ, Scott MP. 89.  1999. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22:103–14 [Google Scholar]
  90. Wefers AK, Warmuth-Metz M, Poschl J, von Bueren AO, Monoranu CM. 90.  et al. 2014. Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. Acta Neuropathol 127:931–33 [Google Scholar]
  91. Wu X, Northcott PA, Dubuc A, Dupuy AJ, Shih DJ. 91.  et al. 2012. Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature 482:529–33 [Google Scholar]
  92. Yang Z-J, Ellis T, Markant SL, Read T-A, Kessler JD. 92.  et al. 2008. Medulloblastoma can be initiated by deletion of patched in lineage-restricted progenitors or stem cells. Cancer Cell 14:135–45 [Google Scholar]
  93. Zecevic N, Rakic P. 93.  1976. Differentiation of Purkinje cells and their relationship to other components of developing cerebellar cortex in man. J. Comp. Neurol. 167:27–47 [Google Scholar]
  94. Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB. 94.  et al. 1999. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J. Clin. Oncol. 17:832–45 [Google Scholar]
  95. Zhukova N, Ramaswamy V, Remke M, Martin DC, Castelo-Branco P. 95.  et al. 2014. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma. Acta Neuropathol. Commun. 2:3 [Google Scholar]
  96. Zhukova N, Ramaswamy V, Remke M, Pfaff E, Shih DJ. 96.  et al. 2013. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J. Clin. Oncol. 31:2927–35 [Google Scholar]
/content/journals/10.1146/annurev-genom-091416-035434
Loading
/content/journals/10.1146/annurev-genom-091416-035434
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error