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http://dx.doi.org/10.3340/jkns.2018.0028

Medulloblastoma in the Molecular Era  

Kuzan-Fischer, Claudia Miranda (Developmental & Stem Cell Biology Program, The Hospital for Sick Children)
Juraschka, Kyle (Developmental & Stem Cell Biology Program, The Hospital for Sick Children)
Taylor, Michael D. (Developmental & Stem Cell Biology Program, The Hospital for Sick Children)
Publication Information
Journal of Korean Neurosurgical Society / v.61, no.3, 2018 , pp. 292-301 More about this Journal
Abstract
Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.
Keywords
Medulloblastoma; Pediatrics; Neurosurgery; Neoplasms; Computational biology;
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1 Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, et al. : Molecular subgroups of medulloblastoma: an international metaanalysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, group 3, and group 4 medulloblastomas. Acta Neuropathol 123 : 473-484, 2012   DOI
2 Korshunov A, Remke M, Kool M, Hielscher T, Northcott PA, Williamson D, et al. : Biological and clinical heterogeneity of MYCN-amplified medulloblastoma. Acta Neuropathol 123 : 515-527, 2012   DOI
3 Kuzan-Fischer CM, Guerreiro Stucklin AS, Taylor MD : Advances in genomics explain medulloblastoma behavior at the bedside. Neurosurgery 64(CN_suppl_1) : 21-26, 2017   DOI
4 Lafay-Cousin L, Smith A, Chi SN, Wells E, Madden J, Margol A, et al. : Clinical, pathological, and molecular characterization of infant medulloblastomas treated with sequential high-dose chemotherapy. Pediatr Blood Cancer 63 : 1527-1534, 2016   DOI
5 Lau J, Schmidt C, Markant SL, Taylor MD, Wechsler-Reya RJ, Weiss WA : Matching mice to malignancy: molecular subgroups and models of medulloblastoma. Childs Nerv Syst 28 : 521-532, 2012   DOI
6 Law N, Smith ML, Greenberg M, Bouffet E, Taylor MD, Laughlin S, et al. : Executive function in paediatric medulloblastoma: the role of cerebrocerebellar connections. J Neuropsychol 11 : 174-200, 2017   DOI
7 MacDonald TJ, Aguilera D, Castellino RC : The rationale for targeted therapies in medulloblastoma. Neuro Oncol 16 : 9-20, 2014
8 Marino S : Medulloblastoma: developmental mechanisms out of control. Trends Mol Med 11 : 17-22, 2005   DOI
9 Milla LA, Arros A, Espinoza N, Remke M, Kool M, Taylor MD, et al. : Neogenin1 is a sonic hedgehog target in medulloblastoma and is necessary for cell cycle progression. Int J Cancer 134 : 21-31, 2014   DOI
10 Mille F, Tamayo-Orrego L, Levesque M, Remke M, Korshunov A, Cardin J, et al. : The Shh receptor Boc promotes progression of early medulloblastoma to advanced tumors. Dev Cell 31 : 34-47, 2014   DOI
11 Morrissy AS, Cavalli FMG, Remke M, Ramaswamy V, Shih DJH, Holgado BL, et al. : Spatial heterogeneity in medulloblastoma. Nat Genet 49 : 780-788, 2017   DOI
12 Morrissy AS, Garzia L, Shih DJ, Zuyderduyn S, Huang X, Skowron P, et al. : Divergent clonal selection dominates medulloblastoma at recurrence. Nature 529 : 351-357, 2016   DOI
13 Moxon-Emre I, Bouffet E, Taylor MD, Laperriere N, Scantlebury N, Law N, et al. : Impact of craniospinal dose, boost volume, and neurologic complications on intellectual outcome in patients with medulloblastoma. J Clin Oncol 32 : 1760-1768, 2014   DOI
14 Moxon-Emre I, Taylor MD, Bouffet E, Hardy K, Campen CJ, Malkin D, et al. : Intellectual outcome in molecular subgroups of medulloblastoma. J Clin Oncol 34 : 4161-4170, 2016   DOI
15 Mumert M, Dubuc A, Wu X, Northcott PA, Chin SS, Pedone CA, et al. : Functional genomics identifies drivers of medulloblastoma dissemination. Cancer Res 72 : 4944-4953, 2012   DOI
16 Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T, et al. : The whole-genome landscape of medulloblastoma subtypes. Nature 547 : 311-317, 2017   DOI
17 Northcott PA, Dubuc AM, Pfister S, Taylor MD : Molecular subgroups of medulloblastoma. Expert Rev Neurother 12 : 871-884, 2012   DOI
18 Northcott PA, Jones DT, Kool M, Robinson GW, Gilbertson RJ, Cho YJ, et al. : Medulloblastomics: the end of the beginning. Nat Rev Cancer 12 : 818-834, 2012   DOI
19 Northcott PA, Korshunov A, Pfister SM, Taylor MD : The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 8 : 340-351, 2012   DOI
20 Tang Y, Gholamin S, Schubert S, Willardson MI, Lee A, Bandopadhayay P, et al. : Epigenetic targeting of hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med 20 : 732-740, 2014   DOI
21 Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X, et al. : Mutations in SUFU predispose to medulloblastoma. Nat Genet 31 : 306-310, 2002   DOI
22 Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. : Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123 : 465-472, 2012   DOI
23 Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, et al. : Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 24 : 1924-1931, 2006   DOI
24 Taylor MD, Zhang X, Liu L, Hui CC, Mainprize TG, Scherer SW, et al. : Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling. Oncogene 23 : 4577-4583, 2004   DOI
25 Taylor RE, Bailey CC, Robinson KJ, Weston CL, Walker DA, Ellison D, et al. : Outcome for patients with metastatic (M2-3) medulloblastoma treated with SIOP/UKCCSG PNET-3 chemotherapy. Eur J Cancer 41 : 727-734, 2005   DOI
26 Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, et al. : Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis. Lancet Oncol 17 : 484-495, 2016   DOI
27 Traenka C, Remke M, Korshunov A, Bender S, Hielscher T, Northcott PA, et al. : Role of LIM and SH3 protein 1 (LASP1) in the metastatic dissemination of medulloblastoma. Cancer Res 70 : 8003-8014, 2010   DOI
28 Taipale J, Cooper MK, Maiti T, Beachy PA : Patched acts catalytically to suppress the activity of smoothened. Nature 418 : 892-897, 2002   DOI
29 Faria CC, Agnihotri S, Mack SC, Golbourn BJ, Diaz RJ, Olsen S, et al. : Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma. Oncotarget 6 : 21718-21729, 2015
30 Dubuc AM, Remke M, Korshunov A, Northcott PA, Zhan SH, Mendez-Lago M, et al. : Aberrant patterns of H3K4 and H3K27 histone lysine methylation occur across subgroups in medulloblastoma. Acta Neuropathol 125 : 373-384, 2013   DOI
31 Faria CC, Golbourn BJ, Dubuc AM, Remke M, Diaz RJ, Agnihotri S, et al. : Foretinib is effective therapy for metastatic sonic hedgehog medulloblastoma. Cancer Res 75 : 134-146, 2015
32 Gajjar A, Pfister SM, Taylor MD, Gilbertson RJ : Molecular insights into pediatric brain tumors have the potential to transform therapy. Clin Cancer Res 20 : 5630-5640, 2014   DOI
33 Gajjar A, Pizer B : Role of high-dose chemotherapy for recurrent medulloblastoma and other CNS primitive neuroectodermal tumors. Pediatr Blood Cancer 54 : 649-651, 2010   DOI
34 Gajjar AJ, Robinson GW : Medulloblastoma-translating discoveries from the bench to the bedside. Nat Rev Clin Oncol 11 : 714-722, 2014   DOI
35 Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D, et al. : Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol 23 : 7621-7631, 2005   DOI
36 Wang X, Dubuc AM, Ramaswamy V, Mack S, Gendoo DMA, Remke M, et al. : Medulloblastoma subgroups remain stable across primary and metastatic compartments. Acta Neuropathol 129 : 449-457, 2015   DOI
37 Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, Eden C, et al. : Subtypes of medulloblastoma have distinct developmental origins. Nature 468 : 1095-1099, 2010   DOI
38 Grill J, Sainte-Rose C, Jouvet A, Gentet JC, Lejars O, Frappaz D, et al. : Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children. Lancet Oncol 6 : 573-580, 2005   DOI
39 Triscott J, Lee C, Foster C, Manoranjan B, Pambid MR, Berns R, et al. : Personalizing the treatment of pediatric medulloblastoma: polo-like kinase 1 as a molecular target in high-risk children. Cancer Res 73 : 6734-6744, 2013   DOI
40 Venkataraman S, Alimova I, Balakrishnan I, Harris P, Birks DK, Griesinger A, et al. : Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget 5 : 2355-2371, 2014
41 Wang X, Ramaswamy V, Remke M, Mack SC, Dubuc AM, Northcott PA, et al. : Intertumoral and intratumoral heterogeneity as a barrier for effective treatment of medulloblastoma. Neurosurgery 60 Suppl 1 : 57-63, 2013   DOI
42 Whittier KL, Boese EA, Gibson-Corley KN, Kirby PA, Darbro BW, Qian Q, et al. : G-protein coupled receptor expression patterns delineate medulloblastoma subgroups. Acta Neuropathol Commun 1 : 66, 2013   DOI
43 Wu X, Northcott PA, Dubuc A, Dupuy AJ, Shih DJ, Witt H, et al. : Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature 482 : 529-533, 2012   DOI
44 Yauch RL, Dijkgraaf GJP, Alicke B, Januario T, Ahn CP, Holcomb T, et al. : Smoothened mutation confers resistance to a hedgehog pathway inhibitor in medulloblastoma. Science 326 : 572-574, 2009   DOI
45 Zapotocky M, Mata-Mbemba D, Sumerauer D, Liby P, Lassaletta A, Zamecnik J, et al. : Differential patterns of metastatic dissemination across medulloblastoma subgroups. J Neurosurg Pediatr, 2017 [Epub ahead of print]
46 Zhou L, Picard D, Ra YS, Li M, Northcott PA, Hu Y, et al. : Silencing of thrombospondin-1 is critical for myc-induced metastatic phenotypes in medulloblastoma. Cancer Res 70 : 8199-8210, 2010   DOI
47 Holgado BL, Guerreiro Stucklin A, Garzia L, Daniels C, Taylor MD : Tailoring medulloblastoma treatment through genomics: making a change, one subgroup at a time. Annu Rev Genomics Hum Genet 18 : 143-166, 2017   DOI
48 Guerreiro Stucklin AS, Ramaswamy V, Daniels C, Taylor MD : Review of molecular classification and treatment implications of pediatric brain tumors. Curr Opin Pediatr 30 : 3-9, 2018   DOI
49 Henrich N, Marra CA, Gastonguay L, Mabbott D, Malkin D, Fryer C, et al. : De-escalation of therapy for pediatric medulloblastoma: trade-offs between quality of life and survival. Pediatr Blood Cancer 61 : 1300-1304, 2014   DOI
50 Hoff von K, Hinkes B, Gerber NU, Deinlein F, Mittler U, Urban C, et al. : Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT'91. Eur J Cancer 45 : 1209-1217, 2009   DOI
51 Hovestadt V, Jones DT, Picelli S, Wang W, Kool M, Northcott PA, et al. : Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature 510 : 537-541, 2014   DOI
52 Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, et al. : Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 488 : 49-56, 2012   DOI
53 Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, et al. : Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29 : 1408-1414, 2011   DOI
54 Northcott PA, Lee C, Zichner T, Stutz AM, Erkek S, Kawauchi D, et al. : Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511 : 428-434, 2014   DOI
55 Northcott PA, Nakahara Y, Wu X, Feuk L, Ellison DW, Croul S, et al. : Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat Genet 41 : 465-472, 2009   DOI
56 Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V, et al. : Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 25 : 393-405, 2014   DOI
57 Johansson G, Andersson U, Melin B : Recent developments in brain tumor predisposing syndromes. Acta Oncol 55 : 401-411, 2016   DOI
58 Jones DTW, Jager N, Kool M, Zichner T, Hutter B, Sultan M, et al. : Dissecting the genomic complexity underlying medulloblastoma. Nature 488 : 100-105, 2012   DOI
59 Kim J, Aftab BT, Tang JY, Kim D, Lee AH, Rezaee M, et al. : Itraconazole and arsenic trioxide inhibit hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists. Cancer Cell 23 : 23-34, 2013   DOI
60 Northcott PA, Shih DJ, Remke M, Cho YJ, Kool M, Hawkins C, et al. : Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. Acta Neuropathol 123 : 615-626, 2012   DOI
61 Pambid MR, Berns R, Adomat HH, Hu K, Triscott J, Maurer N, et al. : Overcoming resistance to Sonic hedgehog inhibition by targeting p90 ribosomal S6 kinase in pediatric medulloblastoma. Pediatr Blood Cancer 61 : 107-115, 2014   DOI
62 Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, et al. : The genetic landscape of the childhood cancer medulloblastoma. Science 331 : 435-439, 2011   DOI
63 Pei Y, Liu KW, Wang J, Garancher A, Tao R, Esparza LA, et al. : HDAC and PI3K antagonists cooperate to inhibit growth of MYC-driven medulloblastoma. Cancer Cell 29 : 311-323, 2016   DOI
64 Perreault S, Ramaswamy V, Achrol AS, Chao K, Liu TT, Shih D, et al. : MRI surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol 35 : 1263-1269, 2014   DOI
65 Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, et al. : Novel mutations target distinct subgroups of medulloblastoma. Nature 488 : 43-48, 2012   DOI
66 Ramaswamy V, Taylor MD : Medulloblastoma: from myth to molecular. J Clin Oncol 35 : 2355-2363, 2017   DOI
67 Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J, et al. : Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148 : 59-71, 2012   DOI
68 Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, et al. : Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 29 : 2717-2723, 2011   DOI
69 Robinson GW, Orr BA, Wu G, Gururangan S, Lin T, Qaddoumi I, et al. : Vismodegib exerts targeted efficacy against recurrent sonic hedgehogsubgroup medulloblastoma: results from phase II Pediatric Brain Tumor Consortium studies PBTC-025B and PBTC-032. J Clin Oncol 33 : 2646- 2654, 2015   DOI
70 Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, et al. : Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 361 : 1173-1178, 2009   DOI
71 Ramaswamy V, Northcott PA, Taylor MD : FISH and chips: the recipe for improved prognostication and outcomes for children with medulloblastoma. Cancer Genet 204 : 577-588, 2011   DOI
72 Rusert JM, Wu X, Eberhart CG, Taylor MD, Wechsler-Reya RJ : SnapShot: medulloblastoma. Cancer Cell 26 : 940-940.e1, 2014   DOI
73 Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, et al. : Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352 : 978-986, 2005   DOI
74 Sabel M, Fleischhack G, Tippelt S, Gustafsson G, Doz F, Kortmann R, et al. : Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study. J Neurooncol 129 : 515-524, 2016   DOI
75 Zhukova N, Ramaswamy V, Remke M, Martin DC, Castelo-Branco P, Zhang CH, et al. : WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma. Acta Neuropathol Commun 2 : 174, 2014   DOI
76 Zhukova N, Ramaswamy V, Remke M, Pfaff E, Shih DJ, Martin DC, et al. : Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol 31 : 2927-2935, 2013   DOI
77 Pfaff E, Remke M, Sturm D, Benner A, Witt H, Milde T, et al. : TP53 mutation is frequently associated with CTNNB1 mutation or MYCN amplification and is compatible with long-term survival in medulloblastoma. J Clin Oncol 28 : 5188-5196, 2010   DOI
78 Pietsch T, Schmidt R, Remke M, Korshunov A, Hovestadt V, Jones DT, et al. : Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort. Acta Neuropathol 128 : 137-149, 2014   DOI
79 Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, et al. : Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488 : 106-110, 2012   DOI
80 Ramaswamy V, Nor C, Taylor MD : p53 and Meduloblastoma. Cold Spring Harb Perspect Med 6 : a026278, 2015
81 Ramaswamy V, Remke M, Adamski J, Bartels U, Tabori U, Wang X, et al. : Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients? Neuro Oncol 18 : 291-297, 2016   DOI
82 Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, et al. : Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol 131 : 821-831, 2016   DOI
83 Ramaswamy V, Remke M, Bouffet E, Faria CC, Perreault S, Cho YJ, et al. : Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 14 : 1200-1207, 2013   DOI
84 Ramaswamy V, Remke M, Shih D, Wang X, Northcott PA, Faria CC, et al. : Duration of the pre-diagnostic interval in medulloblastoma is subgroup dependent. Pediatr Blood Cancer 61 : 1190-1194, 2014   DOI
85 Shih DJ, Northcott PA, Remke M, Korshunov A, Ramaswamy V, Kool M, et al. : Cytogenetic prognostication within medulloblastoma subgroups. J Clin Oncol 32 : 886-896, 2014   DOI
86 Schneider C, Ramaswamy V, Kulkarni AV, Rutka JT, Remke M, Tabori U, et al. : Clinical implications of medulloblastoma subgroups: incidence of CSF diversion surgery. J Neurosurg Pediatr 15 : 236-242, 2015   DOI
87 Schwalbe EC, Lindsey JC, Nakjang S, Crosier S, Smith AJ, Hicks D, et al. : Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study. Lancet Oncol 18 : 958-971, 2017   DOI
88 Schwalbe EC, Williamson D, Lindsey JC, Hamilton D, Ryan SL, Megahed H, et al. : DNA methylation profiling of medulloblastoma allows robust subclassification and improved outcome prediction using formalin-fixed biopsies. Acta Neuropathol 125 : 359-371, 2013   DOI
89 Badodi S, Dubuc A, Zhang X, Rosser G, Da Cunha Jaeger M, Kameda- Smith MM, et al. : Convergence of BMI1 and CHD7 on ERK signaling in medulloblastoma. Cell Rep 21 : 2772-2784, 2017   DOI
90 Alimova I, Venkataraman S, Harris P, Marquez VE, Northcott PA, Dubuc A, et al. : Targeting the enhancer of zeste homologue 2 in medulloblastoma. Int J Cancer 131 : 1800-1809, 2012   DOI
91 Bandopadhayay P, Bergthold G, Nguyen B, Schubert S, Gholamin S, Tang Y, et al. : BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res 20 : 912-925, 2014   DOI
92 Berman DM, Karhadkar SS, Hallahan AR, Pritchard JI, Eberhart CG, Watkins DN, et al. : Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 297 : 1559-1561, 2002   DOI
93 Buonamici S, Williams J, Morrissey M, Wang A, Guo R, Vattay A, et al. : Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med 2 : 51ra70, 2010
94 Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, et al. : Intertumoral heterogeneity within medulloblastoma subgroups. Cancer Cell 31 : 737-754.e6, 2017   DOI
95 Cohen BH, Geyer JR, Miller DC, Curran JG, Zhou T, Holmes E, et al. : 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, 2015   DOI
96 Dubuc AM, Northcott PA, Kenney AM, Taylor MD : Calculating a cure for cancer: managing medulloblastoma MATH1-ematically. Expert Rev Neurother 10 : 1489-1492, 2010   DOI
97 Tabori U, Baskin B, Shago M, Alon N, Taylor MD, Ray PN, et al. : Universal poor survival in children with medulloblastoma harboring somatic TP53 mutations. J Clin Oncol 28 : 1345-1350, 2010   DOI
98 Skowron P, Ramaswamy V, Taylor MD : Genetic and molecular alterations across medulloblastoma subgroups. J Mol Med (Berl) 93 : 1075-1084, 2015   DOI
99 Suryo Rahmanto A, Savov V, Brunner A, Bolin S, Weishaupt H, Malyukova A, et al. : FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma. Embo J 35 : 2192-2212, 2016   DOI
100 Swartling FJ, Grimmer MR, Hackett CS, Northcott PA, Fan QW, Goldenberg DD, et al. : Pleiotropic role for MYCN in medulloblastoma. Genes Dev 24 : 1059-1072, 2010   DOI
101 Taipale J, Chen JK, Cooper MK, Wang B, Mann RK, Milenkovic L, et al. : Effects of oncogenic mutations in smoothened and patched can be reversed by cyclopamine. Nature 406 : 1005-1009, 2000   DOI