Signaling pathway and molecular subgroups of medulloblastoma

International Journal of Clinical and Experimental Pathology

Volumn 6, Issue 7, 2013, Pages 1211-1222

  Li, Kay Ka Wai ^a   Lau, Kin Mang ^a   Ng, Ho Keung ^a  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

Medulloblastoma; Molecular subgroups; Signaling pathway

Indexed keywords

ANTINEOPLASTIC AGENT; TUMOR MARKER;

ANIMAL; CEREBELLUM TUMOR; CLASSIFICATION; DRUG EFFECT; DRUG RESISTANCE; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETICS; GENOMICS; HUMAN; MEDULLOBLASTOMA; METABOLISM; METHODOLOGY; MOLECULAR SUBGROUPS; MOLECULARLY TARGETED THERAPY; PATHOLOGY; PATIENT SELECTION; PERSONALIZED MEDICINE; PHENOTYPE; REVIEW; SIGNAL TRANSDUCTION; SIGNALING PATHWAY; TREATMENT OUTCOME;

MEDULLOBLASTOMA; MOLECULAR SUBGROUPS; SIGNALING PATHWAY;

ANIMALS; ANTINEOPLASTIC AGENTS; CEREBELLAR NEOPLASMS; DRUG RESISTANCE, NEOPLASM; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; GENOMICS; HUMANS; INDIVIDUALIZED MEDICINE; MEDULLOBLASTOMA; MOLECULAR TARGETED THERAPY; PATIENT SELECTION; PHENOTYPE; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84883023860     PISSN: None     EISSN: 19362625     Source Type: Journal    
DOI: None     Document Type: Review

References (92)

1. Dhall G. Medulloblastoma. J Child Neurol 2009; 24: 1418-30.
2. Jozwiak J, Grajkowska W, Wlodarski P. Pathogenesis of medulloblastoma and current treatment outlook. Med Res Rev 2007; 27: 869-90.
3. Rickert CH, Paulus W. Epidemiology of central nervous system tumors in childhood and adolescence based on the new WHO classification. Childs Nerv Syst 2001; 17: 503-11.
4. Giangaspero F, Eberhart CG, Ellison DW, et al. Medulloblastoma. In: Louis DN, Ohgaki H, Wiestler OD, editors. WHO Classification of Tumours of the Nervous System. Lyon: IARC; 2007.
5. Ellison DW, Clifford SC, Gajjar A, Gilbertson RJ. What's new in neuro-oncology? Recent advances in medulloblastoma. Eur J Paediatr Neurol 2003; 7: 53-66.
6. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. 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 prospecmulticentre trial. Lancet Oncol 2006; 7: 813-820.
7. Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol 2006; 24: 4202-4208.
8. Mulhern RK, Palmer SL, Merchant TE, Wallace D, Kocak M, Brouwers P, Krull K, Chintagumpala M, Stargatt R, Ashley DM, Tyc VL, Kun L, Boyett J, Gajjar A. Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma. J Clin Oncol 2005; 23: 5511-9.
9. 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: 357-65.
10. Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by sonic hedgehog. Neuron 1999; 22: 103-114.
11. Dey J, Ditzler S, Knoblaugh SE, Hatton BA, Schelter JM, Cleary MA, Mecham B, Rorke-Adams LB, Olson JM. A distinct smoothened mutation causes severe cerebellar developmental defects and medulloblastoma in a novel transgenic mouse model. Mol Cell Biol 2012; 32: 4104-15.
12. Cowan R, Hoban P, Kelsey A, Birch JM, Gattamaneni R, Evans DG. The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma. Br J Cancer 1997; 76: 141-5.
13. De Bont JM, Packer RJ, Michiels EM, den Boer ML, Pieters R. Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective. Neuro Oncol 2008; 10: 1040-60.
14. Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JM. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br J Cancer 1991; 64: 959-61.
15. Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996; 85: 841-51.
16. Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 1996; 272: 1668-71.
17. Reifenberger J, Wolter M, Weber RG, Megahed M, Ruzicka T, Lichter P, Reifenberger G. Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 1998; 58: 1798-803.
18. Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X, Agatep R, Chiappa S, Gao L, Lowrance A, Hao A, Goldstein AM, Stavrou T, Scherer SW, Dura WT, Wainwright B, Squire JA, Rutka JT, Hogg D. Mutations in SUFU predispose to medulloblastoma. Nat Genet 2002; 31: 306-10.
19. Hooper JE, Scott MP. The Drosophila patched gene encodes a putative membrane protein required for segmental patterning. Cell 1989; 59: 751-65.
20. Nakano Y, Guerrero I, Hidalgo A, Taylor A, Whittle JR, Ingham PW. A protein with several possible membrane-spanning domains encoded by the Drosophila segment polarity gene patched. Nature 1989; 341: 508-13.
21. Carpenter D, Stone DM, Brush J, Ryan A, Armanini M, Frantz G, Rosenthal A, de Sauvage FJ. Characterization of two patched receptors for the vertebrate hedgehog protein family. Proc Natl Acad Sci U S A 1998; 95: 13630-4.
22. Gilbertson RJ, Ellison DW. The origins of medulloblastoma subtypes. Annu Rev Pathol 2008; 3: 341-65.
23. Stecca B, Ruizi Altaba A. The therapeutic potential of modulators of the Hedgehog-Gli signaling pathway. J Biol 2002; 1: 9.
24. Epstein DJ, Marti E, Scott MP, McMahon AP. Antagonizing cAMP-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathway. Development 1996; 122: 2885-94.
25. Kenney AM, Rowitch DH. Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol Cell Biol 2000; 20: 9055-67.
26. Kenney AM, Cole MD, Rowitch DH. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 2003; 130: 15-28.
27. Goodrich LV, Milenković L, Higgins KM, Scott MP. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 1997; 277: 1109-13.
28. Lee Y, Kawagoe R, Sasai K, Li Y, Russell HR, Curran T, McKinnon PJ. Loss of suppressor-of-fused function promotes tumorigenesis. Oncogene 2007; 26: 6442-7.
29. Hatton BA, Villavicencio EH, Tsuchiya KD, Pritchard JI, Ditzler S, Pullar B, Hansen S, Knoblaugh SE, Lee D, Eberhart CG, Hallahan AR, Olson JM. The Smo/Smo model: hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread. Cancer Res 2008; 68: 1768-76.
30. Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA, Russell TL, Ellenbogen RG, Bernstein ID, Beachy PA, Olson JM. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res 2004; 64: 7794-800.
31. Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B, Burger PC, Wood PA, Taqi F, Booker SV, Petersen GM, Offerhaus JA, Tersmette AC, Giardiello FM, Vogelstein B, Kinzler KW. The molecular basis of Turcot's syndrome. N Engl J Med 1995; 332: 839-47.
32. Baeza N, Masuoka J, Kleihues P, Ohgaki H. AXIN1 mutations but not deletions in cerebellar medulloblastomas. Oncogene 2003; 22: 632-6.
33. Eberhart CG, Tihan T, Burger PC. Nuclear localization and mutation of beta-catenin in medulloblastomas. J Neuropathol Exp Neurol 2000; 59: 333-7.
34. Huang H, Mahler-Araujo BM, Sankila A, Chimelli L, Yonekawa Y, Kleihues P, Ohgaki H. APC mutations in sporadic medulloblastomas. Am J Pathol 2000; 156: 433-7.
35. Koch A, Waha A, Tonn JC, Sörensen N, Berthold F, Wolter M, Reifenberger J, Hartmann W, Friedl W, Reifenberger G, Wiestler OD, Pietsch T. Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors. Int J Cancer 2001; 93: 445-9.
36. Zurawel RH, Chiappa SA, Allen C, Raffel C. Sporadic medulloblastomas contain oncogenic beta-catenin mutations. Cancer Res 1998; 58: 896-9.
37. Barker N, Hurlstone A, Musisi H, Miles A, Bienz M, Clevers H. The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation. EMBO J 2001; 20: 4935-43.
38. Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 1996; 382: 638-42.
39. Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 2006; 281: 22429-33.
40. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW. Identification of c-MYC as a target of the APC pathway. Science 1998; 281: 1509-12.
41. Mosimann C, Hausmann G, Basler K. Beta-catenin hits chromatin: regulation of Wnt target gene activation. Nat Rev Mol Cell Biol 2009; 10: 276-86.
42. Novak A, Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci 1999; 56: 523-537.
43. Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999; 398: 422-6.
44. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, Eden C, Kranenburg TA, Hogg T, Poppleton H, Martin J, Finkelstein D, Pounds S, Weiss A, Patay Z, Scoggins M, Ogg R, Pei Y, Yang ZJ, Brun S, Lee Y, Zindy F, Lindsey JC, Taketo MM, Boop FA, Sanford RA, Gajjar A, Clifford SC, Roussel MF, McKinnon PJ, Gutmann DH, Ellison DW, Wechsler-Reya R, Gilbertson RJ. Subtypes of medulloblastoma have distinct developmental origins. Nature 2010; 468: 1095-9.
45. Rogers HA, Sousa S, Salto C, Arenas E, Coyle B, Grundy RG. WNT/β-catenin pathway activation in Myc immortalised cerebellar progenitor cells inhibits neuronal differentiation and generates tumours resembling medulloblastoma. Br J Cancer 2012; 107: 1144-52.
46. del Amo FF, Gendron-Maguire M, Swiatek PJ, Jenkins NA, Copeland NG, Gridley T. Cloning, analysis, and chromosomal localization of Notch-1, a mouse homolog of Drosophila Notch. Genomics 1993; 15: 259-264.
47. Lardelli M, Lendahl U. Motch A and motch B: two mouse Notch homologues coexpressed in a wide variety of tissues. Exp Cell Res 1993; 204: 364-372.
48. Lardelli M, Dahlstrand J, Lendahl U. The novel Notch homologue mouse Notch 3 lacks specific epidermal growth factor-repeats and is expressed in proliferating neuroepithelium. Mech Dev 1994; 46: 123-136.
49. Uyttendaele H, Marazzi G, Wu G, Yan Q, Sassoon D, Kitajewski J. Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene. Development 1996; 122: 2251-2259.
50. Weinmaster G, Roberts VJ, Lemke G. Notch2: a second mammalian Notch gene. Development 1992; 116: 931-941.
51. Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell 1997; 90: 281-291.
52. Kageyama R, Ohtsuka T, Tomita K. The bHLH gene Hes1 regulates differentiation of multiple cell types. Mol Cells 2000; 10: 1-7.
53. Fan X, Mikolaenko I, Elhassan I, Ni X, Wang Y, Ball D, Brat DJ, Perry A, Eberhart CG. Notch1 and notch2 have opposite effects on embryoducednal brain tumor growth. Cancer Res 2004; 64: 7787-93.
54. Xu P, Yu S, Jiang R, Kang C, Wang G, Jiang H, Pu P. Differential expression of Notch family members in astrocytomas and medulloblastomas. Pathol Oncol Res 2009; 15: 703-10.
55. Giangaspero F, Rigobello L, Badiali M, Loda M, Andreini L, Basso G, Zorzi F, Montaldi A. Large-cell medulloblastomas. A distinct variant with highly aggressive behavior. Am J Surg Pathol 1992; 16: 687-93.
56. Brown HG, Kepner JL, Perlman EJ, Friedman HS, Strother DR, Duffner PK, Kun LE, Goldthwaite PT, Burger PC. "Large cell/anaplastic" medulloblastomas: a Pediatric Oncology Group Study. J Neuropathol Exp Neurol 2000; 59: 857-65.
57. 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.
58. McCabe MG, Bäcklund LM, Leong HS, Ichimura K, Collins VP. Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma. Neuro Oncol 2011; 13: 376-83.
59. Tabori U, Baskin B, Shago M, Alon N, Taylor MD, Ray PN, Bouffet E, Malkin D, Hawkins C. Universal poor survival in children with medulloblastoma harboring somatic TP53 mutations. J Clin Oncol 2010; 28: 1345-50.
60. Clifford SC, Lusher ME, Lindsey JC, Langdon JA, Gilbertson RJ, Straughton D, Ellison DW. 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: 2666-70.
61. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, Ellison DW, Lichter P, Gilbertson RJ, Pomeroy SL, Kool M, Pfister SM. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 2012; 123: 465-72.
62. Jones DT, Jäger N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stütz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schüller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rössler J, Ebinger M, Schuhmann MU, Frühwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P. Dissecting the genomic complexity underlying medulloblastoma. Nature 2012; 488: 100-5.
63. Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, Carneiro MO, Carter SL, Cibulskis K, Erlich RL, Greulich H, Lawrence MS, Lennon NJ, McKenna A, Meldrim J, Ramos AH, Ross MG, Russ C, Shefler E, Sivachenko A, Sogoloff B, Stojanov P, Tamayo P, Mesirov JP, Amani V, Teider N, Sengupta S, Francois JP, Northcott PA, Taylor MD, Yu F, Crabtree GR, Kautzman AG, Gabriel SB, Getz G, Jäger N, Jones DT, Lichter P, Pfister SM, Roberts TM, Meyerson M, Pomeroy SL, Cho YJ. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 2012; 488: 106-10.
64. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, Phoenix TN, Hedlund E, Wei L, Zhu X, Chalhoub N, Baker SJ, Huether R, Kriwacki R, Curley N, Thiruvenkatam R, Wang J, Wu G, Rusch M, Hong X, Becksfort J, Gupta P, Ma J, Easton J, Vadodaria B, Onar-Thomas A, Lin T, Li S, Pounds S, Paugh S, Zhao D, Kawauchi D, Roussel MF, Finkelstein D, Ellison DW, Lau CC, Bouffet E, Hassall T, Gururangan S, Cohn R, Fulton RS, Fulton LL, Dooling DJ, Ochoa K, Gajjar A, Mardis ER, Wilson RK, Downing JR, Zhang J, Gilbertson RJ. Novel mutations target distinct subgroups of medulloblastoma. Nature 2012; 488: 43-8.
65. Kool M, Korshunov A, Remke M, Jones DT, Schlanstein M, Northcott PA, Cho YJ, Koster J, Schouten-van Meeteren A, van Vuurden D, Clifford SC, Pietsch T, von Bueren AO, Rutkowski S, McCabe M, Collins VP, Bäcklund ML, Haberler C, Bourdeaut F, Delattre O, Doz F, Ellison DW, Gilbertson RJ, Pomeroy SL, Taylor MD, Lichter P, Pfister SM. 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.
66. Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, Benner A, von Deimling A, Scheurlen W, Perry A, Croul S, Kulozik AE, Lichter P, Taylor MD, Pfister SM, Korshunov A. Adult medulloblastoma comprises three major molecular variants. J Clin Oncol 2011; 29: 2717-23.
67. Sadighi Z, Vats T, Khatua S. Childhood medulloblastoma: the paradigm shift in molecular stratification and treatment profile. J Child Neurol 2012; 27: 1302-7.
68. Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsić A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 2008; 3: e3088.
69. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, Rutka JT, Pfister S, Taylor MD. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 2011; 29: 1408-14.
70. Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, Chintagumpala M, Adesina A, Ashley DM, Kellie SJ, Taylor MD, Curran T, Gajjar A, Gilbertson RJ. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol 2006; 24: 1924-31.
71. Northcott PA, Hielscher T, Dubuc A, Mack S, Shih D, Remke M, Al-Halabi H, Albrecht S, Jabado N, Eberhart CG, Grajkowska W, Weiss WA, Clifford SC, Bouffet E, Rutka JT, Korshunov A, Pfister S, Taylor MD. Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinct. Acta Neuropathol 2011; 122: 231-40.
72. Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stütz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fèvre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognár L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van MeirEG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 2012; 488: 49-56.
73. Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G, Kenney AM, Brat DJ, Perry A, Yong WH, Taylor RE, Bailey S, Clifford SC, Gilbertson RJ. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol 2011; 121: 381-96.
74. Ellison DW. Childhood medulloblastoma: novel approaches to the classification of a heterogeneous disease. Acta Neuropathol 2010; 120: 305-16.
75. Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, Berhoukim R, Amani V, Goumnerova L, Eberhart CG, Lau CC, Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, Pomeroy SL. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol 2011; 29: 1424-30.
76. Choi YJ, Lee SG. The DEAD-box RNA helicase DDX3 interacts with DDX5, co-localizes with it in the cytoplasm during the G2/M phase of the cycle, and affects its shuttling during mRNP export. J Cell Biochem 2012; 113: 985-96.
77. Lai MC, Lee YH, Tarn WY. The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control. Mol Biol Cell 2008; 19: 3847-58.
78. Rosner A, Rinkevich B. The DDX3 subfamily of the DEAD box helicases: divergent roles as unveiled by studying different organisms and in vitro assays. Curr Med Chem 2007; 14: 2517-25.
79. Northcott PA, Korshunov A, Pfister SM, Taylor MD. The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 2012; 8: 340-51.
80. Swigut T, Wysocka J. H3K27 demethylases, at long last. Cell 2007; 131: 29-32.
81. Yoo KH, Hennighausen L. EZH2 methyltransferase and H3K27 methylation in breast cancer. Int J Biol Sci 2012; 8: 59-65.
82. Remke M, Hielscher T, Korshunov A, Northcott PA, Bender S, Kool M, Westermann F, Benner A, Cin H, Ryzhova M, Sturm D, Witt H, Haag D, Toedt G, Wittmann A, Schöttler A, von BuerenAO, von Deimling A, Rutkowski S, Scheurlen W, Kulozik AE, Taylor MD, Lichter P, Pfister SM. FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma. J Clin Oncol 2011; 29: 3852-61.
83. Ferretti E, De Smaele E, Po A, Di Marcotullio L, Tosi E, Espinola MS, Di Rocco C, Riccardi R, Giangaspero F, Farcomeni A, Nofroni I, Laneve P, Gioia U, Caffarelli E, Bozzoni I, Screpanti I, Gulino A. MicroRNA profiling in human medulloblastoma. Int J Cancer 2009; 124: 568-77.
84. Lv SQ, Kim YH, Giulio F, Shalaby T, Nobusawa S, Yang H, Zhou Z, Grotzer M, Ohgaki H. Genetic alterations in microRNAs in medulloblastomas. Brain Pathol 2012; 22: 230-9.
85. Pang JC, Kwok WK, Chen Z, Ng HK. Oncogenic role of microRNAs in brain tumors. Acta Neuropathol 2009; 117: 599-611.
86. Li KK, Pang JC, Ching AK, Wong CK, Kong X, Wang Y, Zhou L, Chen Z, Ng HK. miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. Hum Pathol 2009; 40: 1234-43.
87. Li KK, Pang JC, Lau KM, Zhou L, Mao Y, Wang Y, Poon WS, Ng HK. MiR-383 is Downregulated in Medulloblastoma and Targets Peroxiredoxin 3 (PRDX3). Brain Pathol 2012. doi: 10.1111/bpa.12014. [Epub ahead of print].
88. Pierson J, Hostager B, Fan R, Vibhakar R. Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol 2008; 90: 1-7.
89. Venkataraman S, Alimova I, Fan R, Harris P, Foreman N, Vibhakar R. MicroRNA 128a increases intracellular ROS level by targeting Bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. PLoS One 2010; 5: e10748.
90. Weeraratne SD, Amani V, Teider N, Pierre-Francois J, Winter D, Kye MJ, Sengupta S, Archer T, Remke M, Bai AH, Warren P, Pfister SM, Steen JA, Pomeroy SL, Cho YJ. Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma. Acta Neuropathol 2012; 123: 539-52.
91. Diede SJ, Guenthoer J, Geng LN, Mahoney SE, Marotta M, Olson JM, Tanaka H, Tapscott SJ. DNA methylation of developmental genes in pediatric medulloblastomas identified by denaturation analysis of methylation differences. Proc Natl Acad Sci U S A 2010; 107: 234-9.
92. Vibhakar R, Foltz G, Yoon JG, Field L, Lee H, Ryu GY, Pierson J, Davidson B, Madan A. Dickkopf-1 is an epigenetically silenced candidate tumor suppressor gene in medulloblastoma. Neuro Oncol 2007; 9: 135-44.