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

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Abstract

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 Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers.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.

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References

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    PubMed  PubMed Central  Google Scholar 

  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 5:2666–2670

    Article  CAS  PubMed  Google Scholar 

  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 20:19–29

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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. 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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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. 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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ramaswamy V, Nor C, Taylor MD (2015) p53 and Meduloblastoma. Cold Spring Harbor Perspect Med. doi:10.1101/cshperspect.a026278

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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. 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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 17:832–845

    CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Division of Haematology/Oncology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

      Vijay Ramaswamy & Eric Bouffet

    2. Department of Pediatric Oncology, Hematology, and Clinical Immunology, University Hospital Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany

      Marc Remke

    3. Department of Pediatric Neuro-Oncogenomics, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Düsseldorf, Germany

      Marc Remke

    4. Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK

      Simon Bailey & Steven C. Clifford

    5. Department of Paediatric, Adolescents and Young Adults Oncology, Curie Institute, and University Paris Descartes, Paris, France

      Francois Doz

    6. Division of Pediatric Neurooncology (B062), DKFZ, and German Cancer Consortium (DKTK), Heidelberg, Germany

      Marcel Kool & Stefan M. Pfister

    7. Department of Pediatric and Adolescent Oncology, Institut Gustave-Roussy, Villejuif, France

      Christelle Dufour & Gilles Vassal

    8. Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Heidelberg, Heidelberg, Germany

      Till Milde, Olaf Witt & Stefan M. Pfister

    9. Clinical Cooperation Unit Pediatric Oncology (G340), DKFZ, Heidelberg, Germany

      Till Milde & Olaf Witt

    10. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

      Katja von Hoff & Stefan Rutkowski

    11. Neuropathology, University of Bonn, Bonn, Germany

      Torsten Pietsch

    12. St. Jude’s Research Hospital, Memphis, TN, USA

      Paul A. Northcott, Amar Gajjar & Giles W. Robinson

    13. Aix-Marseille Université, Inserm, CRO2 UMR_S 911, 27 bd Jean Moulin, 13385, Marseille Cedex 05, France

      Laetitia Padovani

    14. Department of Pediatric Hematology and Oncology, AP-HM, Marseille, France

      Nicolas André

    15. Fondazione IRCCS “Istituto Nazionale dei Tumori”, Milan, Italy

      Maura Massimino

    16. Department of Oncology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK

      Barry Pizer

    17. Department of Neurology, Children’s National Medical Center, Washington, DC, USA

      Roger Packer

    18. Division of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada

      Michael D. Taylor

    19. Department of Neurology, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

      Scott L. Pomeroy

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    1. Vijay Ramaswamy
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    Correspondence to Vijay Ramaswamy or Marc Remke.

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    V. Ramaswamy and M. Remke contributed equally to this work.

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    Ramaswamy, V., Remke, M., Bouffet, E. et al. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol 131, 821–831 (2016). https://doi.org/10.1007/s00401-016-1569-6

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