Pediatric medulloblastoma - update on molecular classification driving targeted therapies

Frontiers in Oncology

Volumn 4 JUL, Issue , 2014, Pages

  DeSouza, Ruth Mary ^a   Benjamin R T Jones, ^b   Lowis, Stephen P ^c   Kurian, Kathreena M ^c  

^a KING S COLLEGE HOSPITAL   (United Kingdom)

^b ROYAL BOLTON HOSPITAL   (United Kingdom)

^c UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

Classification; Medulloblastoma; Molecular; Pediatric; Therapies

Indexed keywords

BETA CATENIN; CYCLOPAMINE; HISTONE DEACETYLASE INHIBITOR; PROTEIN PATCHED 1; SARIDEGIB; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR EZH2; VISMODEGIB; WNT PROTEIN;

AGE; CANCER CLASSIFICATION; CELL PROLIFERATION; GENE AMPLIFICATION; GENE MUTATION; HISTOLOGY; HUMAN; IMMUNOHISTOCHEMISTRY; MEDULLOBLASTOMA; MOLECULARLY TARGETED THERAPY; PROTEIN EXPRESSION; REVIEW; RISK ASSESSMENT; SIGNAL TRANSDUCTION;

EID: 84904595972     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2014.00176     Document Type: Review

References (70)

1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO Classification of Tumours of the Central Nervous System. Lyon: IARC (2007).
2. Pizer BL, Clifford SC. The potential impact of tumour biology on improved clinical practice formedulloblastoma: progress towards biologically driven clinical trials. Br J Neurosurg (2009) 23(4):364-75. doi: 10.1080/02688690903121807
3. Wilne S, Collier J, Kennedy C, Jenkins A, Grout J, Mackie S, et al. Progression from first symptom to diagnosis in childhood brain tumors. Eur J Pediatr (2012) 171(1):87-93. doi:10.1007/s00431-011-1485-7
4. Lamont JM, McManamy CS, Pearson AD, Clifford SC, Ellison DW. Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clin Cancer Res (2004) 10:5482-93. doi:10.1158/1078-0432.CCR-03-0721
5. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol (2012) 123:465-72. doi:10.1007/s00401-011-0922-z
6. Giangaspero F, Perilongo G, Fondelli MP, Brisigotti M, Carollo C, Burnelli R, et al. Medulloblastoma with extensive nodularity: a variant with favorable prognosis. J Neurosurg (1999) 91:971-7. doi:10.3171/jns.1999.91.6.0971
7. Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, et al. 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 (2012) 123:473-84. doi:10.1007/s00401-012-0958-8
8. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol (2011) 29:1408-14. doi:10.1200/JCO.2009.27.4324
9. Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One (2008) 3(8):e3088. doi:10.1371/journal.pone.0003088
10. Chang CH, Housepian EM, Herbert C Jr. An operative staging system and a megavoltage radiotherapeutic technique for cerebellar medulloblastas. Radiology (1969) 93(6):1351-9.
11. Haberler C, Slavc I, Czech T, Gelpi E, Heinzl H, Budka H, et al. Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome. Eur J Cancer (2006) 42(17):2996-3003. doi:10.1016/j.ejca.2006.05.038
12. Giangaspero F, Wellek S, Masuoka J, Gessi M, Kleihues P, Ohgaki H. Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol (2006) 112(1):5-12. doi:10.1007/s00401-006-0064-x
13. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, et al. Novel mutations target distinct subgroups of medulloblastoma. Nature (2012) 488(7409):43-8. doi:10.1038/nature11213
14. Ellison DW, Kocak M, Dalton J, Megahed H, Lusher ME, Ryan SL, et al. Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical, pathologic, and molecular variables. J Clin Oncol (2011) 29:1400-7. doi:10.1200/JCO.2010.30.2810
15. Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nat Lett. Available from: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11329.html
16. MAGIC - Medulloblastoma Advanced. Genomics International Consortium Stratifying and Targeting Pediatric Medulloblastoma through Genomics. Available from: http://www.bcgsc.ca/project/magic
17. Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol (2011) 29:1424-30. doi:10.1200/JCO.2010.28.5148
18. Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol (2011) 121(3):381-96. doi:10.1007/s00401-011-0800-8
19. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, Eden C, et al. Subtypes of medulloblastoma have distinct developmental origins. Nature (2010) 468:1095-9. doi:10.1038/nature09587
20. Baryawno N, Sveinbjörnsson B, Eksborg S, Chen CS, Kogner P, Johnsen JI. Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth. Cancer Res (2010) 70(1):266-76. doi:10.1158/0008-5472.CAN-09-0578
21. Chiang C, Litingtung Y, Lee E, Young KE, Corden JL, Westphal H, et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature (1996) 383:407-13. doi:10.1038/383407a0
22. Mimeault M, Batra SK. Frequent deregulations in the hedgehog signaling network and cross-talks with the epidermal growth factor receptor pathway involved in cancer progression and targeted therapies. Pharmacol Rev (2010) 62(3):497-524. doi:10.1124/pr.109.002329
23. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med (2009) 361(12):1164-72. doi:10.1056/NEJMoa0905360
24. 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 (2009) 361(12):1173-8. doi:10.1056/NEJMoa0902903
25. Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science (2009) 326:572-4. doi:10.1126/science.1179386
26. Li X, Deng W, Lobo-Ruppert SM, Ruppert JM. Gli1 acts through Snail and E-cadherin to promote nuclear signalling by ß-catenin. Oncogene (2007) 26:4489-98. doi:10.1038/sj.onc.1210241
27. Katoh Y, Katoh M. Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med (2009) 9(7):873-86. doi:10.2174/156652409789105570
28. Lee MJ, Hatton BA, Villavicencio EH, Khanna PC, Friedman SD, Ditzler S, et al. Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model. Proc Natl Acad Sci U S A (2012) 109(20):7859-64. doi:10.1073/pnas.1114718109
29. Beauchamp EM, Ringer L, Bulut G, Sajwan KP, Hall MD, Lee YC, et al. Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway. J Clin Invest (2011) 121(1):148-60. doi:10.1172/JCI42874
30. Leary SE, Zhou T, Holmes E, Geyer JR, Miller DC. Histology predicts a favorable outcome in young children with desmoplastic medulloblastoma: a report from the children's oncology group. Cancer (2011) 117(14):3262-7. doi:10.1002/cncr.25856
31. Rieken S, Gaiser T, Mohr A, Welzel T, Witt O, Kulozik AE, et al. Outcome and prognostic factors of desmoplastic medulloblastoma treated within a multidisciplinary treatment concept. BMC Cancer (2010) 10:450. doi:10.1186/1471-2407-10-450
32. Eberhart CG, Kratz J, Wang Y, Summers K, Stearns D, Cohen K, et al. Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol (2004) 63(5):441-9.
33. Adamson DC, Shi Q, Wortham M, Northcott PA, Di C, Duncan CG, et al. OTX is critical for the maintenance and progression of classic medulloblastoma. Cancer Res (2010) 70(1):181-91. doi:10.1158/0008-5472.CAN-09-2331
34. Milde T, Oehme I, Korshunov A, Kopp-Schneider A, Remke M, Northcott P, et al. HDAC5 and HDAC9 in medulloblastoma: novel markers for risk stratification and role in tumour cell growth. Clin Cancer Res (2010) 16:3240-52. doi:10.1158/1078-0432.CCR-10-0395
35. Furchert SE, Lanvers-Kaminsky C, Juürgens H, Jung M, Loidl A, Frühwald MC. Inhibitors of histone deacetylases as potential therapeutic tools for high-risk embryonal tumors of the nervous system of childhood. Int J Cancer (2007) 120:1787-94. doi:10.1002/ijc.22401
36. Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, et al. The genetic landscape of the childhood cancer medulloblastoma. Science (2011) 331:435-9. doi:10.1126/science.1198056
37. Yuh GE, Loredo LN, Yonemoto LT, Bush DA, Shahnazi K, Preston W, et al. Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young children. Cancer J (2004) 10(6):386-90. doi:10.1097/00130404-200411000-00009
38. 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 (2005) 41(5):727-34. doi:10.1016/j.ejca.2004.12.017
39. Maddrey AM, Bergeron JA, Lombardo ER, McDonald NK, Mulne AF, Barenberg PD, et al. Neuropsychological performance and quality of life of 10 year survivors of childhood medulloblastoma. J Neurooncol (2005) 72(3):245-53. doi:10.1007/s11060-004-3009-z
40. von Hoff 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 (2009) 45(7):1209-17. doi:10.1016/j.ejca.2009.01.015
41. Frange P, Alapetite C, Gaboriaud G, Bours D, Zucker JM, Zerah M, et al. From childhood to adulthood: long-term outcome of medulloblastoma patients. The Institut Curie experience (1980-2000). J Neurooncol (2009) 95(2):271-9. doi:10.1007/s11060-009-9927-z
42. Ribi K, Relly C, Landolt MA, Alber FD, Boltshauser E, Grotzer MA. Outcome of medulloblastoma in children: long-term complications and quality of life. Neuropediatrics (2005) 36(6):357-65. doi:10.1055/s-2005-872880
43. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, et al. 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 (2006) 7(10):813-20. doi:10.1016/S1470-2045(06)70867-1
44. von Bueren AO, von Hoff K, Pietsch T, Gerber NU, Warmuth-Metz M, Deinlein F, et al. Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. Neuro Oncol (2011) 13(6):669-79. doi:10.1093/neuonc/nor025
45. Polakis P. Drugging Wnt signalling in cancer. EMBO J (2012) 31:2737-46. doi:10.1038/emboj.2012.126
46. Lorenz A, Deutschmann M, Ahlfeld J, Prix C, Koch A, Smits R, et al. Severe alterations of cerebellar cortical development after constitutive activation of Wnt signaling in granule neuron precursors. Mol Cell Biol (2011) 31(16):3326-38. doi:10.1128/MCB.05718-11
47. Pei Y, Brun SN, Markant SL, Lento W, Gibson P, Taketo MM, et al. WNT signaling increases proliferation and impairs differentiation of stem cells in the developing cerebellum. Development (2012) 139(10):1724-33. doi:10.1242/dev.050104
48. Silva RD, Marie SK, Uno M, Matushita H, Wakamatsu A, Rosemberg S, et al. CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants. Clinics (Sao Paulo) (2013) 68(2):167-72. doi:10.6061/clinics/2013(02)OA08
49. Rogers HA, Sousa S, Salto C, Arenas E, Coyle B, Grundy RG. WNT/ß-catenin pathway activation in Myc immortalised cerebellar progenitor cells inhibits neuronal differentiation and generates tumors resembling medulloblastoma. Br J Cancer (2012) 107(7):1144-52. doi:10.1038/bjc.2012.377
50. Cimmino F, Scoppettuolo MN, Carotenuto M, De Antonellis P, Dato VD, De Vita G, et al. Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/ß-catenin signalling. J Neurooncol (2012) 106:59-70. doi:10.1007/s11060-011-0645-y
51. Yang J, Wu J, Tan C, Klein PS. PP2A:B56epsilon is required for Wnt/beta-catenin signaling during embryonic development. Development (2003) 130(23):5569-78. doi:10.1242/dev.00762
52. Lee EY, Ji H, Ouyang Z, Zhou B, Ma W, Vokes SA, et al. Hedgehog pathway-regulated gene networks in cerebellum development and tumorigenesis. Proc Natl Acad Sci U S A (2010) 107(21):9736-41. doi:10.1073/pnas.1004602107
53. Haldipur P, Bharti U, Govindan S, Sarkar C, Iyengar S, Gressens P, et al. Expression of Sonic hedgehog during cell proliferation in the human cerebellum. Stem Cells Dev (2012) 21(7):1059-68. doi:10.1089/scd.2011.0206
54. Pritchard JI, Olson JM. Methylation of PTCH1, the Patched-1 gene, in a panel of primary medulloblastomas. Cancer Genet Cytogenet (2008) 180(1):47-50. doi:10.1016/j.cancergencyto.2007.09.008
55. Lee Y, Kawagoe R, Sasai K, Li Y, Russell HR, Curran T, et al. Loss of suppressor-of-fused function promotes tumorigenesis. Oncogene (2007) 26(44):6442-7. doi:10.1038/sj.onc.1210467
56. Brugières L, Remenieras A, Pierron G, Varlet P, Forget S, Byrde V, et al. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J Clin Oncol (2012) 30(17):2087-93. doi:10.1200/JCO.2011.38.7258
57. 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 (2000) 406(6799):1005-9. doi:10.1038/35023008
58. Drenkhahn SK, Jackson GA, Slusarz A, Starkey NJ, Lubahn DB. Inhibition of Hedgehog/Gli signaling by botanicals: a review of compounds with potential hedgehog pathway inhibitory activities. Curr Cancer Drug Targets (2013) 13(5):580-95. doi:10.2174/15680096113139990003
59. Del Carratore R, Carpi A, Beffy P, Lubrano V, Giorgetti L, Maserti BE, et al. Itraconazole inhibits HMEC-1 angiogenesis. Biomed Pharmacother (2012) 66(4):312-7. doi:10.1016/j.biopha.2011.11.004
60. 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 (2013) 125(3):373-84. doi:10.1007/s00401-012-1070-9
61. Spiller SE, Ditzler SH, Pullar BJ, Olson JM. Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA). J Neurooncol (2008) 87:133-41. doi:10.1007/s11060-007-9505-1
62. Hyman JM, Firestone AJ, Heine VM, Zhao Y, Ocasio CA, Han K, et al. Small-molecule inhibitors reveal multiple strategiesfor Hedgehog pathway blockade. Proc Natl Acad Sci U S A (2009) 106(33):14132-7. doi:10.1073/pnas.0907134106
63. Results from A Prospective Trial of Proton Radiotherapy for Medulloblastoma: Clinical Outcome Including Hearing and Neurocognitive. Available from: http://www.oncolink.org/conferences/article.cfm?id=2185
64. Packer RJ, Macdonald T, Vezina G, Keating R, Santi M. Medulloblastoma and primitive neuroectodermal tumors. Handb Clin Neurol (2012) 105:529-48. doi:10.1016/B978-0-444-53502-3.00007-0
65. Clifford SC, Lusher ME, Lindsey JC, Langdon JA, Gilbertson RJ, Straughton D, et al. Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblastomas associated with a favorable prognosis. Cell Cycle (2006) 5(22):2666-70. doi:10.4161/cc.5.22.3446
66. Attard TM, Giglio P, Koppula S, Snyder C, Lynch HT. Brain tumors in individuals with familial adenomatous polyposis: a cancer registry experience and pooled case report analysis. Cancer (2007) 109(4):761-6. doi:10.1002/cncr.22475
67. Zakaria R, Ellenbogen J, Graham C, Pizer B, Mallucci C, Kumar R. A decision analysis tool for the assessment of posterior fossa tumor surgery outcomes in children-the "Liverpool Neurosurgical Complication Causality Assessment Tool". Childs Nerv Syst (2013) 29(8):1277-83. doi:10.1007/s00381-013-2065-0
68. Schwalbe EC, Lindsey JC, Straughton D, Hogg TL, Cole M, Megahed H, et al. Rapid diagnosis of medulloblastoma molecular subgroups. Clin Cancer Res (2011) 17(7):1883-94. doi:10.1158/1078-0432.CCR-10-2210
69. 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 (2013) 14(12):1200-7. doi:10.1016/S1470-2045(13)70449-2
70. Baryawno N, Sveinbjörnsson B, Kogner P, Johnsen JI. Medulloblastoma: a disease with disorganized developmental signaling cascades. Cell Cycle (2010) 9(13):2548-54. doi:10.4161/cc.9.13.12170