Acta Neuropathologica

, Volume 131, Issue 6, pp 821–831 | Cite as

Risk stratification of childhood medulloblastoma in the molecular era: the current consensus

  • Vijay Ramaswamy
  • Marc Remke
  • Eric Bouffet
  • Simon Bailey
  • Steven C. Clifford
  • Francois Doz
  • Marcel Kool
  • Christelle Dufour
  • Gilles Vassal
  • Till Milde
  • Olaf Witt
  • Katja von Hoff
  • Torsten Pietsch
  • Paul A. Northcott
  • Amar Gajjar
  • Giles W. Robinson
  • Laetitia Padovani
  • Nicolas André
  • Maura Massimino
  • Barry Pizer
  • Roger Packer
  • Stefan Rutkowski
  • Stefan M. Pfister
  • Michael D. Taylor
  • Scott L. Pomeroy
Consensus Paper


Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3–17). Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90 % survival), average (standard) risk (75–90 % survival), high risk (50–75 % survival) and very high risk (<50 % survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low-risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently completed clinical trials, this consensus can serve as an outline for prioritization of certain molecular subsets of tumors to define and validate risk groups as a basis for future clinical trials.


Medulloblastoma Subgroups WNT SHH Group 3 Group 4 p53 Genomics Outcomes 


  1. 1.
    Bandopadhayay P, Bergthold G, Nguyen B, Schubert S, Gholamin S, Tang Y et al (2014) BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res 20:912–925. doi: 10.1158/1078-0432.ccr-13-2281 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bull KS, Spoudeas HA, Yadegarfar G, Kennedy CR (2007) Reduction of health status 7 years after addition of chemotherapy to craniospinal irradiation for medulloblastoma: a follow-up study in PNET 3 trial survivors on behalf of the CCLG (formerly UKCCSG). J Clin Oncol 25:4239–4245. doi: 10.1200/jco.2006.08.7684 CrossRefPubMedGoogle Scholar
  3. 3.
    Camara-Costa H, Resch A, Kieffer V, Lalande C, Poggi G, Kennedy C et al (2015) Neuropsychological outcome of children treated for standard risk medulloblastoma in the PNET4 European randomized controlled trial of hyperfractionated versus standard radiation therapy and maintenance chemotherapy. Int J Radiat Oncol Biol Phys 92:978–985. doi: 10.1016/j.ijrobp.2015.04.023 CrossRefPubMedGoogle Scholar
  4. 4.
    Cho Y-J, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H et al (2011) Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol 29:1424–1430. doi: 10.1200/JCO.2010.28.5148 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Clifford SC, Lannering B, Schwalbe EC, Hicks D, Toole KO, Nicholson SL et al. (2015) Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: Results from the multi-center HIT-SIOP-PNET4 clinical trial. Oncotarget 6:38827–38839. doi: 10.18632/oncotarget.5149 PubMedPubMedCentralGoogle Scholar
  6. 6.
    Clifford SC, Lusher ME, Lindsey JC, Langdon JA, Gilbertson RJ, Straughton D 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 5:2666–2670CrossRefPubMedGoogle Scholar
  7. 7.
    Cochrane DD, Gustavsson B, Poskitt KP, Steinbok P, Kestle JR (1994) The surgical and natural morbidity of aggressive resection for posterior fossa tumors in childhood. Pediatr Neurosurg 20:19–29CrossRefPubMedGoogle Scholar
  8. 8.
    Donahue B, Marymont MA, Kessel S, Iandoli MK, Fitzgerald T, Holmes E et al (2012) Radiation therapy quality in CCG/POG intergroup 9961: implications for craniospinal irradiation and the posterior fossa boost in future medulloblastoma trials. Front Oncol 2:185. doi: 10.3389/fonc.2012.00185 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Ecker J, Oehme I, Mazitschek R, Korshunov A, Kool M, Hielscher T et al (2015) Targeting class I histone deacetylase 2 in MYC amplified group 3 medulloblastoma. Acta Neuropathol Commun 3:22. doi: 10.1186/s40478-015-0201-7 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G et al (2011) Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol 121:381–396. doi: 10.1007/s00401-011-0800-8 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ellison DW, Kocak M, Dalton J, Megahed H, Lusher ME, Ryan SL et al (2011) Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical, pathologic, and molecular variables. J Clin Oncol 29:1400–1407. doi: 10.1200/jco.2010.30.2810 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ellison DW, Onilude OE, Lindsey JC, Lusher ME, Weston CL, Taylor RE 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. doi: 10.1200/jco.2005.01.5479 CrossRefPubMedGoogle Scholar
  13. 13.
    Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE 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 7:813–820. doi: 10.1016/S1470-2045(06)70867-1 CrossRefPubMedGoogle Scholar
  14. 14.
    Gandola L, Massimino M, Cefalo G, Solero C, Spreafico F, Pecori E et al (2008) Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma. J Clin Oncol 27:566–571. doi: 10.1200/JCO.2008.18.4176 CrossRefPubMedGoogle Scholar
  15. 15.
    Garre ML, Cama A, Bagnasco F, Morana G, Giangaspero F, Brisigotti M et al (2009) Medulloblastoma variants: age-dependent occurrence and relation to Gorlin syndrome—a new clinical perspective. Clin Cancer Res 15:2463–2471. doi: 10.1158/1078-0432.ccr-08-2023 CrossRefPubMedGoogle Scholar
  16. 16.
    Goschzik T, Zur Muhlen A, Kristiansen G, Haberler C, Stefanits H, Friedrich C et al (2014) Molecular stratification of medulloblastoma: Comparison of histological and genetic methods to detect Wnt activated tumors. Neuropathol Appl Neurobiol. doi: 10.1111/nan.12161
  17. 17.
    Gottardo NG, Hansford JR, McGlade JP, Alvaro F, Ashley DM, Bailey S 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. doi: 10.1007/s00401-013-1213-7 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hill RM, Kuijper S, Lindsey JC, Petrie K, Schwalbe EC, Barker K et al (2015) Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. Cancer Cell 27:72–84. doi: 10.1016/j.ccell.2014.11.002 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Jones DT, Jager N, Kool M, Zichner T, Hutter B, Sultan M et al (2012) Dissecting the genomic complexity underlying medulloblastoma. Nature 488:100–105. doi: 10.1038/nature11284 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Kennedy C, Bull K, Chevignard M, Culliford D, Dorr HG, Doz F et al (2014) Quality of survival and growth in children and young adults in the PNET4 European controlled trial of hyperfractionated versus conventional radiation therapy for standard-risk medulloblastoma. Int J Radiat Oncol Biol Phys 88:292–300. doi: 10.1016/j.ijrobp.2013.09.046 CrossRefPubMedGoogle Scholar
  21. 21.
    Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V et al (2014) Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 25:393–405. doi: 10.1016/j.ccr.2014.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA 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 123:473–484. doi: 10.1007/s00401-012-0958-8 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P et al (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3:e3088. doi: 10.1371/journal.pone.0003088 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Korshunov A, Remke M, Kool M, Hielscher T, Northcott PA, Williamson D et al (2012) Biological and clinical heterogeneity of MYCN-amplified medulloblastoma. Acta Neuropathol 123:515–527. doi: 10.1007/s00401-011-0918-8 CrossRefPubMedGoogle Scholar
  25. 25.
    Kunder R, Jalali R, Sridhar E, Moiyadi A, Goel N, Goel A et al (2013) Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas. Neuro Oncol 15:1644–1651. doi: 10.1093/neuonc/not123 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lannering B, Rutkowski S, Doz F, Pizer B, Gustafsson G, Navajas A et al (2012) Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial. J Clin Oncol 30:3187–3193. doi: 10.1200/jco.2011.39.8719 CrossRefPubMedGoogle Scholar
  27. 27.
    Milde T, Lodrini M, Savelyeva L, Korshunov A, Kool M, Brueckner LM et al (2012) HD-MB03 is a novel Group 3 medulloblastoma model demonstrating sensitivity to histone deacetylase inhibitor treatment. J Neurooncol 110:335–348. doi: 10.1007/s11060-012-0978-1 CrossRefPubMedGoogle Scholar
  28. 28.
    Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang X, Skowron P et al (2016) Divergent clonal selection dominates medulloblastoma at recurrence. Nature 529:351–357. doi: 10.1038/nature16478 CrossRefPubMedGoogle Scholar
  29. 29.
    Moxon-Emre I, Bouffet E, Taylor MD, Laperriere N, Scantlebury N, Law N et al. (2014) Impact of craniospinal dose, boost volume, and neurologic complications on intellectual outcome in patients with medulloblastoma. J Clin Oncol 32:1760–1768. doi: 10.1200/jco.2013.52.3290 CrossRefPubMedGoogle Scholar
  30. 30.
    Mulhern RK, Palmer SL, Merchant TE, Wallace D, Kocak M, Brouwers P et al (2005) Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol 23:5511–5519. doi: 10.1200/JCO.2005.00.703 CrossRefPubMedGoogle Scholar
  31. 31.
    Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ, Cho YJ et al (2012) Medulloblastomics: the end of the beginning. Nat Rev Cancer 12:818–834. doi: 10.1038/nrc3410 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S et al (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29:1408–1414. doi: 10.1200/JCO.2009.27.4324 CrossRefPubMedGoogle Scholar
  33. 33.
    Northcott PA, Lee C, Zichner T, Stutz AM, Erkek S, Kawauchi D et al (2014) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428–434. doi: 10.1038/nature13379 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T et al (2012) Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 488:49–56. doi: 10.1038/nature11327 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Northcott PA, Shih DJ, Remke M, Cho YJ, Kool M, Hawkins C et al (2012) Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol 123:615–626. doi: 10.1007/s00401-011-0899-7 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL et al (2006) Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 24:4202–4208. doi: 10.1200/JCO.2006.06.4980 CrossRefPubMedGoogle Scholar
  37. 37.
    Packer RJ, Zhou T, Holmes E, Vezina G, Gajjar A (2012) Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children’s Oncology Group trial A9961. Neuro Oncol. doi: 10.1093/neuonc/nos267
  38. 38.
    Pei Y, Liu KW, Wang J, Garancher A, Tao R, Esparza LA et al (2016) HDAC and PI3K antagonists cooperate to inhibit growth of MYC-driven medulloblastoma. Cancer Cell 29:311–323. doi: 10.1016/j.ccell.2016.02.011 CrossRefPubMedGoogle Scholar
  39. 39.
    Pietsch T, Schmidt R, Remke M, Korshunov A, Hovestadt V, Jones DT et al (2014) Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol 128:137–149. doi: 10.1007/s00401-014-1276-0 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J et al (2012) Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488:106–110. doi: 10.1038/nature11329 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ramaswamy V, Nor C, Taylor MD (2015) p53 and Meduloblastoma. Cold Spring Harbor Perspect Med. doi: 10.1101/cshperspect.a026278
  42. 42.
    Ramaswamy V, Remke M, Adamski J, Bartels U, Tabori U, Wang X et al (2016) Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients? Neuro Oncol 18:291–297. doi: 10.1093/neuonc/nou357 CrossRefPubMedGoogle Scholar
  43. 43.
    Ramaswamy V, Remke M, Bouffet E, Faria CC, Perreault S, Cho YJ et al (2013) Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 14:1200–1207. doi: 10.1016/s1470-2045(13)70449-2 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Remke M, Hielscher T, Korshunov A, Northcott PA, Bender S, Kool M et al (2011) FSTL5 Is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma. J Clin Oncol 29:3852–3861. doi: 10.1200/jco.2011.36.2798 CrossRefPubMedGoogle Scholar
  45. 45.
    Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A et al (2011) Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 29:2717–2723. doi: 10.1200/jco.2011.34.9373 CrossRefPubMedGoogle Scholar
  46. 46.
    Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L et al (2012) Novel mutations target distinct subgroups of medulloblastoma. Nature 488:43–48. doi: 10.1038/nature11213 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Robinson GW, Orr BA, Wu G, Gururangan S, Lin T, Qaddoumi I 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 33:2646–2654. doi: 10.1200/jco.2014.60.1591 CrossRefPubMedGoogle Scholar
  48. 48.
    Schwalbe EC, Williamson D, Lindsey JC, Hamilton D, Ryan SL, Megahed H et al (2013) DNA methylation profiling of medulloblastoma allows robust subclassification and improved outcome prediction using formalin-fixed biopsies. Acta Neuropathol 125:359–371. doi: 10.1007/s00401-012-1077-2 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Shih DJ, Northcott PA, Remke M, Korshunov A, Ramaswamy V, Kool M et al (2014) Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol 32:886–896. doi: 10.1200/jco.2013.50.9539 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Tamayo P, Cho Y-J, Tsherniak A, Greulich H, Ambrogio L, Schouten-Van Meeteren N et al (2011) Predicting relapse in patients with medulloblastoma by integrating evidence from clinical and genomic features. J Clin Oncol 29:1415–1423. doi: 10.1200/JCO.2010.28.1675 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Tarbell NJ, Friedman H, Polkinghorn WR, Yock T, Zhou T, Chen Z et al (2013) High-risk medulloblastoma: a pediatric oncology group randomized trial of chemotherapy before or after radiation therapy (POG 9031). J Clin Oncol 31:2936–2941. doi: 10.1200/jco.2012.43.9984 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X et al (2002) Mutations in SUFU predispose to medulloblastoma. Nat Genet 31:306–310. doi: 10.1038/ng916 CrossRefPubMedGoogle Scholar
  53. 53.
    Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC et al (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123:465–472. doi: 10.1007/s00401-011-0922-z CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Taylor RE, Bailey CC, Robinson KJ, Weston CL, Ellison D, Ironside J et al (2004) Impact of radiotherapy parameters on outcome in the International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 study of preradiotherapy chemotherapy for M0-M1 medulloblastoma. Int J Radiat Oncol Biol Phys 58:1184–1193. doi: 10.1016/j.ijrobp.2003.08.010 CrossRefPubMedGoogle Scholar
  55. 55.
    Taylor RE, Bailey CC, Robinson KJ, Weston CL, Walker DA, Ellison D et al (2005) Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer 41:727–734. doi: 10.1016/j.ejca.2004.12.017 CrossRefPubMedGoogle Scholar
  56. 56.
    Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S et al (2016) Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol. doi: 10.1016/s1470-2045(15)00581-1
  57. 57.
    Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC et al (2006) Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24:1924–1931. doi: 10.1200/JCO.2005.04.4974 CrossRefPubMedGoogle Scholar
  58. 58.
    Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H et al (2011) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol 12:559–567. doi: 10.1016/s1470-2045(11)70119-x CrossRefPubMedGoogle Scholar
  59. 59.
    Wu X, Northcott PA, Dubuc A, Dupuy AJ, Shih DJ, Witt H et al (2012) Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature 482:529–533. doi: 10.1038/nature10825 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM 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 17:832–845PubMedGoogle Scholar
  61. 61.
    Zhukova N, Ramaswamy V, Remke M, Martin DC, Castelo-Branco P, Zhang CH et al (2014) WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma. Acta Neuropathol Commun 2:174. doi: 10.1186/s40478-014-0174-y CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Zhukova N, Ramaswamy V, Remke M, Pfaff E, Shih DJ, Martin DC et al (2013) Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol 31:2927–2935. doi: 10.1200/jco.2012.48.5052 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Vijay Ramaswamy
    • 1
  • Marc Remke
    • 2
    • 3
  • Eric Bouffet
    • 1
  • Simon Bailey
    • 4
  • Steven C. Clifford
    • 4
  • Francois Doz
    • 5
  • Marcel Kool
    • 6
  • Christelle Dufour
    • 7
  • Gilles Vassal
    • 7
  • Till Milde
    • 8
    • 9
  • Olaf Witt
    • 8
    • 9
  • Katja von Hoff
    • 10
  • Torsten Pietsch
    • 11
  • Paul A. Northcott
    • 12
  • Amar Gajjar
    • 12
  • Giles W. Robinson
    • 12
  • Laetitia Padovani
    • 13
  • Nicolas André
    • 14
  • Maura Massimino
    • 15
  • Barry Pizer
    • 16
  • Roger Packer
    • 17
  • Stefan Rutkowski
    • 10
  • Stefan M. Pfister
    • 6
    • 8
  • Michael D. Taylor
    • 18
  • Scott L. Pomeroy
    • 19
  1. 1.Division of Haematology/OncologyHospital for Sick ChildrenTorontoCanada
  2. 2.Department of Pediatric Oncology, Hematology, and Clinical ImmunologyUniversity Hospital DüsseldorfDüsseldorfGermany
  3. 3.Department of Pediatric Neuro-OncogenomicsGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)DüsseldorfGermany
  4. 4.Northern Institute for Cancer ResearchNewcastle UniversityNewcastle-upon-TyneUK
  5. 5.Department of Paediatric, Adolescents and Young Adults OncologyCurie Institute, and University Paris DescartesParisFrance
  6. 6.Division of Pediatric Neurooncology (B062)DKFZ, and German Cancer Consortium (DKTK)HeidelbergGermany
  7. 7.Department of Pediatric and Adolescent OncologyInstitut Gustave-RoussyVillejuifFrance
  8. 8.Department of Pediatric Oncology, Hematology and Clinical ImmunologyUniversity Hospital HeidelbergHeidelbergGermany
  9. 9.Clinical Cooperation Unit Pediatric Oncology (G340)DKFZHeidelbergGermany
  10. 10.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  11. 11.NeuropathologyUniversity of BonnBonnGermany
  12. 12.St. Jude’s Research HospitalMemphisUSA
  13. 13.Aix-Marseille Université, Inserm, CRO2 UMR_S 911Marseille Cedex 05France
  14. 14.Department of Pediatric Hematology and OncologyAP-HMMarseilleFrance
  15. 15.Fondazione IRCCS “Istituto Nazionale dei Tumori”MilanItaly
  16. 16.Department of OncologyAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  17. 17.Department of NeurologyChildren’s National Medical CenterWashington, DCUSA
  18. 18.Division of NeurosurgeryHospital for Sick ChildrenTorontoCanada
  19. 19.Department of NeurologyBoston Children’s Hospital and Harvard Medical SchoolBostonUSA

Personalised recommendations