The epigenetics of brain tumors

Methods in Molecular Biology

Volumn 863, Issue , 2012, Pages 139-153

  Dubuc, Adrian M ^a   MacK, Stephen ^a   Unterberger, Alexander ^b   Northcott, Paul A ^b   Taylor, Michael D ^a  

^a UNIVERSITY OF TORONTO   (Canada)

^b HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

Differentiation; Ependymoma; Glioblastoma; Global hypomethylation; Medulloblastoma; MicroRNAs; Promoter hypermethylation

Indexed keywords

HISTONE; MICRORNA;

ARTICLE; BRAIN TUMOR; DNA METHYLATION; EPENDYMOMA; GENETIC EPIGENESIS; GENETICS; GLIOBLASTOMA; HUMAN; MEDULLOBLASTOMA; METABOLISM; PHYSIOLOGY;

BRAIN NEOPLASMS; DNA METHYLATION; EPENDYMOMA; EPIGENESIS, GENETIC; GLIOBLASTOMA; HISTONES; HUMANS; MEDULLOBLASTOMA; MICRORNAS;

EID: 84859947992     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-61779-612-8_8     Document Type: Article

References (113)

1. CBTRUS. (2010) 2010 CBTRUS Statistical Report, in Central Brain Tumour Registry of the United States .
2. Ang, C., Gulot, M.C., Ramanakumar, A.V., Roberge, D., and Kavan, P. (2010) Clinical Signifi cance of molecular biomarkers in glioblastoma. Can J Neurol Sci 37, 625-630.
3. Nishikawa, R. (2010) Standard therapy for glioblastoma - A review of where we are. Neurol Med Chir 50, 713-719.
4. Ellison, D. (2010) Childhood medulloblastoma: Novel approaches to the classifi cation of a heterogeneous disease. Acta Neuropathol 120, 305-316.
5. Mack, S.C. and Taylor, M.D. (2009) The genetic and epigenetic basis of ependymoma. Childs Nerv Syst 25, 1195-1201.
6. Christophersen, N.S. and Helin, K. (2010) Epigenetic Control of embryonic stem cell fate. J Exp Med 25, 2287-2295.
7. Baylin, S.B. and Ohm, J.E. (2006) Epigenetic gene silencing in cancer - A mechanism for early oncogenic pathway addiction. Nat Rev Cancer 6, 107-116. (Pubitemid 43361543)
8. Jones, P.A. and Baylin, S.B. (2002) The fundamental role of epigenetic events in cancer. Nat Rev Cancer 3, 415-428. (Pubitemid 34587077)
9. Garinis, G.A., Patrinos, G.P., Spanakis, N.E., and Menounos, P.G. (2002) DNA hypermethylation: When tumour suppressor genes go silent. Hum. Genet. 111, 115-127. (Pubitemid 36075029)
10. Louis, D.N., Ohgaki, H., Wiestler, O.D., Cavenee, W.K., Burger, P.C., Jouvet, A., Scheithauer, B.W., and Kleihues, P. (2007) The 2007 WHO classifi cation of tumours of the central nervous system. Acta Neuropathol 114, 97-109. (Pubitemid 47103521)
11. Schwartzbaum, J.A., Fisher, J.L., Aldape, K.D., and Wrensch, M. (2006) Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol 2, 494-503; quiz 491 p following 516. (Pubitemid 44275725)
12. Stupp, R., Mason, W.P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J., Belanger, K., Brandes, A.A., Marosi, C., Bogdahn, U., Curschmann, J., Janzer, R. C., Ludwin, S. K., Gorlia, T., Allgeier, A., Lacombe, D., Cairncross, J. G., Eisenhauer, E., and Mirimanoff, R. O. (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352, 987-996. (Pubitemid 40349501)
13. Benjamin, R., Capparella, J., and Brown, A. (2003) Classifi cation of glioblastoma multiforme in adults by molecular genetics. Cancer J 9, 82-90.
14. Louis, D. N. (1997) A molecular genetic model of astrocytoma histopathology. Brain Pathol 7, 755-764. (Pubitemid 27234250)
15. Bostrom, J., Cobbers, J. M., Wolter, M., Tabatabai, G., Weber, R. G., Lichter, P., Collins, V. P., and Reifenberger, G. (1998) Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q. Cancer Res. 58, 29-33. (Pubitemid 28027711)
16. Riemenschneider, M. J., Buschges, R., Wolter, M., Reifenberger, J., Bostrom, J., Kraus, J. A., Schlegel, U., and Reifenberger, G. (1999) Amplifi cation and overexpression of the MDM4 (MDMX) gene from 1q32 in a subset of malignant gliomas without TP53 mutation or MDM2 amplifi cation. Cancer Res. 59, 6091-6096. (Pubitemid 30035626)
17. Collins, V. P. (2002) Cellular mechanisms targeted during astrocytoma progression. Cancer Lett 188, 1-7. (Pubitemid 35292322)
18. von Deimling, A., Louis, D. N., and Wiestler, O. D. (1995) Molecular pathways in the formation of gliomas. Glia 15, 328-338.
19. Schmidt, E. E., Ichimura, K., Reifenberger, G., and Collins, V. P. (1994) CDKN2 (p16/MTS1) gene deletion or CDK4 amplifi cation occurs in the majority of glioblastomas. Cancer Res. 54, 6321-6324.
20. Sancho-Martinez, I., and Martin-Villalba, A. (2009) Tyrosine phosphorylation and CD95: A FAScinating switch. Cell Cycle 8, 838-842.
21. Zhu, Y., Guignard, F., Zhao, D., Liu, L., Burns, D. K., Mason, R. P., Messing, A., and Parada, L. F. (2005) Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8, 119-130. (Pubitemid 41132741)
22. Duncan, B. K., and Miller, J. H. (1980) Mutagenic deamination of cytosine residues in DNA. Nature 287, 560-561. (Pubitemid 11232861)
23. Bentivegna, S.S., and Bresnick, E. (1994) Inhibition of human O6-methylguanine-DNA methyltransferase by 5-methylcytosine. Cancer Res. 54, 327-329.
24. Nakamura, M., Watanabe, T., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (2001) Promoter methylation of the DNA repair gene MGMT in astrocytomas is frequently associated with G:C A:T mutations of the TP53 tumor suppressor gene. Carcinogenesis 22, 1715-1719. (Pubitemid 32952152)
25. Fanelli, M., Caprodossi, S., Ricci-Vitiani, L., Porcellini, A., Tomassoni-Ardori, F., Amatori, S., Andreoni, F., Magnani, M., De Maria, R., Santoni, A., Minucci, S., and Pelicci, P.G. (2008) Loss of pericentromeric DNA methylation pattern in human glioblastoma is associated with altered DNA methyltransferases expression and involves the stem cell compartment. Oncogene 27, 358-365.
26. Cadieux, B., Ching, T.T., VandenBerg, S.R., and Costello, J.F. (2006) Genome-wide hypomethylation in human glioblastomas associated with specific copy number alteration, methylenetetrahydrofolate reductase allele status, and increased proliferation. Cancer Res. 66, 8469-8476. (Pubitemid 44449159)
27. Qian, X.C., and Brent, T.P. (1997) Methylation hot spots in the 5 fl anking region denote silencing of the O6-methylguanine-DNA methyltransferase gene. Cancer Res. 57, 3672-3677. (Pubitemid 27381206)
28. Silber, J.R., Mueller, B.A., Ewers, T.G., and Berger, M.S. (1993) Comparison of O6-methylguanine-DNA methyltransferase activity in brain tumors and adjacent normal brain. Cancer Res. 53, 3416-3420. (Pubitemid 23223319)
29. Silber, J. R., Bobola, M. S., Ghatan, S., Blank, A., Kolstoe, D. D., and Berger, M. S. (1998) O6-methylguanine-DNA methyltransferase activity in adult gliomas: Relation to patient and tumor characteristics. Cancer Res. 58, 1068-1073. (Pubitemid 28182481)
30. Belanich, M., Pastor, M., Randall, T., Guerra, D., Kibitel, J., Alas, L., Li, B., Citron, M., Wasserman, P., White, A., Eyre, H., Jaeckle, K., Schulman, S., Rector, D., Prados, M., Coons, S., Shapiro, W., and Yarosh, D. (1996) Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res. 56, 783-788. (Pubitemid 26055468)
31. Jaeckle, K.A., Eyre, H.J., Townsend, J.J., Schulman, S., Knudson, H.M., Belanich, M., Yarosh, D.B., Bearman, S.I., Giroux, D. J. and Schold, S.C. (1998) Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis- chloroethylnitrosourea: A Southwest Oncology Group study. J. Clin. Oncol 16, 3310-3315. (Pubitemid 28481626)
32. Silber, J.R., Blank, A., Bobola, M.S., Ghatan, S., Kolstoe, D.D., and Berger, M.S. (1999) O6-methylguanine-DNA methyltransferasedefi cient phenotype in human gliomas: Frequency and time to tumor progression after alkylating agent-based chemotherapy. Clin. Cancer Res. 5, 807-814. (Pubitemid 29180832)
33. Esteller, M., Garcia-Foncillas, J., Andion, E., Goodman, S.N., Hidalgo, O.F., Vanaclocha, V., Baylin, S. B., and Herman, J. G. (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N. Engl. J. Med. 343, 1350-1354.
34. Hegi, M.E., Diserens, A.C., Gorlia, T., Hamou, M.F., de Tribolet, N., Weller, M., Kros, J.M., Hainfellner, J.A., Mason, W., Mariani, L., Bromberg, J.E., Hau, P., Mirimanoff, R.O., Cairncross, J.G., Janzer, R.C., and Stupp, R. (2005) MGMT gene silencing and benefi t from temozolomide in glioblastoma. N. Engl. J. Med. 352, 997-1003. (Pubitemid 40349502)
35. Nakamura, M., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (2001) Promoter hypermethylation of the RB1 gene in glioblastomas. Lab Invest 81, 77-82. (Pubitemid 32108641)
36. Li, Q., Jedlicka, A., Ahuja, N., Gibbons, M.C., Baylin, S.B., Burger, P. C., and Issa, J. P. (1998) Concordant methylation of the ER and N33 genes in glioblastoma multiforme. Oncogene 16, 3197-3202. (Pubitemid 28318791)
37. Costello, J.F., Berger, M.S., Huang, H.S., and Cavenee, W.K. (1996) Silencing of p16/CDKN2 expression in human gliomas by methylation and chromatin condensation. Cancer Res. 56, 2405-2410. (Pubitemid 26154090)
38. Park, S.H., Jung, K.C., Ro, J.Y., Kang, G.H. and Khang, S.K. (2000) 5 CpG island methylation of p16 is associated with absence of p16 expression in glioblastomas. J Korean Med Sci 15, 555-559.
39. Nakamura, M., Watanabe, T., Klangby, U., Asker, C., Wiman, K., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (2001) p14ARF deletion and methylation in genetic pathways to glioblastomas. Brain Pathol 11, 159-168. (Pubitemid 32198843)
40. Baeza, N., Weller, M., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (2003) PTEN methylation and expression in glioblastomas. Acta Neuropathol 106, 479-485. (Pubitemid 37265852)
41. Wiencke, J. K., Zheng, S., Jelluma, N., Tihan, T., Vandenberg, S., Tamguney, T., Baumber, R., Parsons, R., Lamborn, K.R., Berger, M.S., Wrensch, M.R., Haas-Kogan, D.A., and Stokoe, D. (2007) Methylation of the PTEN promoter defi nes low-grade gliomas and secondary glioblastoma. Neuro Oncol 9, 271-279. (Pubitemid 47169659)
42. Watanabe, T., Huang, H., Nakamura, M., Wischhusen, J., Weller, M., Kleihues, P., and Ohgaki, H. (2002) Methylation of the p73 gene in gliomas. Acta. Neuropathol. 104, 357-362. (Pubitemid 36075399)
43. Horiguchi, K., Tomizawa, Y., Tosaka, M., Ishiuchi, S., Kurihara, H., Mori, M., and Saito, N. (2003) Epigenetic inactivation of RASSF1A candidate tumor suppressor gene at 3p21.3 in brain tumors. Oncogene 22, 7862-7865. (Pubitemid 37485546)
44. Martinez, R., Setien, F., Voelter, C., Casado, S., Quesada, M. P., Schackert, G., and Esteller, M. (2007) CpG island promoter hypermethylation of the pro-Apoptotic gene caspase-8 is a common hallmark of relapsed glioblastoma multiforme. Carcinogenesis 28, 1264-1268. (Pubitemid 47062686)
45. Zhou, H., Miki, R., Eeva, M., Fike, F.M., Seligson, D., Yang, L., Yoshimura, A., Teitell, M.A., Jamieson, C.A., and Cacalano, N.A. (2007) Reciprocal regulation of SOCS 1 and SOCS3 enhances resistance to ionizing radiation in glioblastoma multiforme. Clin. Cancer Res. 13, 2344-2353. (Pubitemid 46698583)
46. Martini, M., Pallini, R., Luongo, G., Cenci, T., Lucantoni, C., and Larocca, L.M. (2008) Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme. Int J Cancer 123, 2955-2960.
47. Teofi li, L., Martini, M., Cenci, T., Guidi, F., Torti, L., Giona, F., Foa, R., Leone, G., and Larocca, L. M. (2008) Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative diseases. Int J Cancer 123, 1586-1592.
48. Gotze, S., Wolter, M., Reifenberger, G., Muller, O., and Sievers, S. (2010) Frequent promoter hypermethylation of Wnt pathway inhibitor genes in malignant astrocytic gliomas. Int J Cancer 126, 2584-2593.
49. Tabu, K., Sasai, K., Kimura, T., Wang, L., Aoyanagi, E., Kohsaka, S., Tanino, M., Nishihara, H., and Tanaka, S. (2008) Promoter hypomethylation regulates CD133 expression in human gliomas. Cell Res 18, 1037-1046.
50. Martinez, R., Martin-Subero, J. I., Rohde, V., Kirsch, M., Alaminos, M., Fernandez, A. F., Ropero, S., Schackert, G., and Esteller, M. (2009) A microarray-based DNA methylation study of glioblastoma multiforme. Epigenetics 4, 255-264.
51. Noushmehr, H., Welsenberger, D.J., Diefes, K., Phillips, H.S., Pujara, K., et al. (2010) Identifi cation of a CpG island methylator phenotype that defi nes a distinct subgroup of gliomas. Cancer Cell 17, 510-522.
52. Abdouh, M., Facchino, S., Chatoo, W., Balasingam, V., Ferreira, J., and Bernier, G. (2009) BMI1 sustains human glioblastoma multiforme stem cell renewal. J Neurosci 29, 8884-8896.
53. Lee, J., Son, M. J., Woolard, K., Donin, N.M., Li, A., Cheng, C.H., Kotliarova, S., Kotliarov, Y., Walling, J., Ahn, S., Kim, M., Totonchy, M., Cusack, T., Ene, C., Ma, H., Su, Q., Zenklusen, J.C., Zhang, W., Maric, D., and Fine, H.A. (2008) Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells. Cancer Cell 13, 69-80. (Pubitemid 350309742)
54. Lucio-Eterovic, A.K., Cortez, M.A., Valera, E.T., Motta, F.J., Queiroz, R.G., Machado, H.R., Carlotti, C.G., Jr., Neder, L., Scrideli, C.A., and Tone, L.G. (2008) Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: Class II and IV are hypoexpressed in glioblastomas. BMC Cancer 8 , 243.
55. Kim, J.H., Shin, J.H., and Kim, I.H. (2004) Susceptibility and radiosensitization of human glioblastoma cells to trichostatin A, a histone deacetylase inhibitor. Int J Radiat Oncol Biol Phys 59, 1174-1180. (Pubitemid 38834312)
56. Kim, M.S., Blake, M., Baek, J.H., Kohlhagen, G., Pommier, Y., and Carrier, F. (2003) Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res. 63, 7291-7300. (Pubitemid 37413470)
57. Egler, V., Korur, S., Failly, M., Boulay, J.L., Imber, R., Lino, M.M., and Merlo, A. (2008) Histone deacetylase inhibition and blockade of the glycolytic pathway synergistically induce glioblastoma cell death. Clin. Cancer Res. 14, 3132-3140.
58. Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B. L., Mak, R. H., Ferrando, A. A., Downing, J. R., Jacks, T., Horvitz, H. R., and Golub, T. R. (2005) MicroRNA expression profi les classify human cancers. Nature 435, 834-838. (Pubitemid 40839735)
59. Ciafre, S.A., Galardi, S., Mangiola, A., Ferracin, M., Liu, C.G., Sabatino, G., Negrini, M., Maira, G., Croce, C.M., and Farace, M.G. (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334, 1351-1358. (Pubitemid 41074723)
60. Gabriely, G., Wurdinger, T., Kesari, S., Esau, C.C., Burchard, J., Linsley, P.S., and Krichevsky, A.M. (2008) MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol. Cell Biol. 28, 5369-5380.
61. Papagiannakopoulos, T., Shapiro, A., and Kosik, K.S. (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 68, 8164-8172.
62. Kim, H., Huang, W., Jiang, X., Pennicooke, B., Park, P.J., and Johnson, M.D. (2010) Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. Proc. Natl. Acad. Sci. USA 107, 2183-2188.
63. Silber, J., Lim, D.A., Petritsch, C., Persson, A.I., Maunakea, A.K., Yu, M., Vandenberg, S.R., Ginzinger, D.G., James, C.D., Costello, J.F., Bergers, G., Weiss, W.A., Alvarez-Buylla, A., and Hodgson, J.G. (2008) miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med 6, 14.
64. Visvanathan, J., Lee, S., Lee, B., Lee, J.W., and Lee, S.K. (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes. Dev. 21, 744-749. (Pubitemid 46572354)
65. Godlewski, J., Nowicki, M.O., Bronisz, A., Williams, S., Otsuki, A., Nuovo, G., Raychaudhury, A., Newton, H.B., Chiocca, E. A., and Lawler, S. (2008) Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 68, 9125-9130.
66. Godlewski, J., Nowicki, M.O., Bronisz, A., Nuovo, G., Palatini, J., De Lay, M., Van Brocklyn, J., Ostrowski, M.C., Chiocca, E.A., and Lawler, S.E. (2010) MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol Cell 37, 620-632.
67. Dubuc, A.M., Northcott, P.A., Mack, S., Witt, H., Pfi ster, S., et al. (2010) The genetics of pediatric brain tumors. Curr Neurol Neurosci Rep 10, 215-223.
68. MacDonald, T. (2008) Aggressive Infantile embryonal tumours. J Child Neurol 23, 1195-1204.
69. Pfaffe, E., Remke, M., Sturm, D., Benner, A., Witt, H. et al. (2010) TP53 Mutation is Frequently Associated with CTNNB1 Mutation or MYCN Amplifi cation and is Compatible with Long-Term Survival in Medulloblastoma. J. Clin. Oncol 28, 5188-5196.
70. Massimino, M., Giangaspero, F., Garrè, M.L., Gandola, L., Poggi, G., Biassoni, V., Gatta, G., Rukowski, S. (2010) Childhood medulloblastoma. Crit Rev Oncol Hematol 79, 65-83.
71. Thompson, M.C., Fuller, C., Hogg, T.L., Dalton, J., Finkelstein, D., et al.(2006) Genomics Identifi es Medulloblastoma Subgroups That Are Enriched for Specific Genetic Alterations. J. Clin. Oncol 24, 1924-1931. (Pubitemid 46638992)
72. Kool, M., Koster, J., Bunt, J., Hasselt, N.E., Lakeman, A., et al.(2008) Integrated Genomics Identifi es Five Medulloblastoma Subtypes with Distinct Genetic Profi les, Pathway Signatures and Clinicopathological Features. PLoS One 3, e3088.
73. Northcott, P.A., Korshunov, A., Witt, H., Hielscher, T., Eberhart, C.G., et al. (2010) Medulloblastoma Comprises Four Distinct Molecular Variants, J. Clin. Oncol 29 , 1408-1414.
74. Pfi ster, S.M., Korshunov, A., Kool, M., Hasselbatt, M., Eberhart, C.G., et al. (2010) Molecular diagnostics of CNS embryonal tumours. Acta. Neuropathol. 120, 553-566.
75. Low, J.A. and de Sauvage, F. (2010) Clinical Experience with Hedgehog Pathway Inhibitors, J. Clin. Oncol 28, 5321-5326.
76. Flatau, E., Bogenmann, E., and Jones, P.A. (1983) Variable 5-methylcytosine levels in Human Tumours Cell Lines and Fresh Pediatric Explants. Cancer Res. 43, 4901-4905. (Pubitemid 13015874)
77. Smiraglia, D.J., Fruhwald, M., Costello, J.F., McCormick, S.P., Dai, Z. et al. (1999) A New Tool for the Rapid Cloning of Amplifi ed and Hypermethylated Human DNA Sequences from Restriction Landmark Genome Scanning Gels. Genomics 58, 254-262. (Pubitemid 29300308)
78. Fruwald, M.C., O'Dorisio, D.M., Dai, Z., Rush, L.J., Krahe, R., et al. (2001) Aberrant Hypermethylation of the Major Breakpoint Cluster Region in 17p11.2 in Medulloblastomas but not Supratentorial PNETs. Genes Chromosomes Cancer 30, 38-47.
79. Fruwald, M.C., O'Dorisio, D.M., Dai, Z., Tanner, S.M., Balster, D.A. et al.(2001) Aberrant promoter methylation of previously unidentifi ed target genes is a common abnormality in medulloblastoma - Implications for tumour biology and potential clinical utility. Oncogene 20, 5033-5042. (Pubitemid 32769793)
80. Zuzak, T.J., Steinhoff, D.F., Sutton, L.N., Phillips, P.C., Eggert, A. et al. (2002) Loss of caspase-8 mRNA expression is common in childhood primitive neuroectodermal brain tumour/medulloblastoma. Eur J Cancer 38, 83-91. (Pubitemid 34031830)
81. Harada, K., Toyooka, S., Maitra, A., Maruyama, R., Toyooka, K.O., et al. (2002) Aberrant promoter methylation and silencing of RASSF1A gene in pediatric tumor and cell lines. Oncogene 21, 4345-4349. (Pubitemid 34753843)
82. Rood, B.R., Zhang, H., Weitman, D.M. and Cogen, P.H. (2002) Hypermethylation of HIC1 and 17p allelic loss in medulloblastoma. Cancer Res. 62, 3794-3797. (Pubitemid 34728863)
83. Lusher, M.E., Lindsey, J., Latif, F., Pearson, A.D., Ellison, D.W. et al. (2002) Biallelic epigenetic inactivation of the RASSF1A tumour suppressor gene in medulloblastoma development. Cancer Res. 62, 5906-5911. (Pubitemid 35204753)
84. Pfi ster, S., Schlaeger, C., Mendrzyk, F., Wittmann, A., Benner, A. et al. (2007) Arraybased profi ling of reference-independent methylation status (aPRIMES) identifi es frequent promoter methylation and consecutive downregulation of ZIC2 in pediatric medulloblastoma. Nucleic Acids Res 35, e51.
85. Ecke, I., Petry, F., Rosenberger, A., Tauber, S., Monkemeyer, S. et al. (2009) Antitumour effect of combined 5-Aza-cytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in pth mutant mice. Cancer Res. 69, 887-895.
86. Suzuki, H., Gabrielson, E., Chen, W., Anbazhagan, R., van Engeland, M., et al. (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nature Genetics 31, 141-149.
87. Lindsey, J.C., Lusher, M., Anderton, J.A., Gilbertson, R.J., Ellison, D.W. et al. (2007) Epigenetic deregulation of multiple S100 family gene family members by differential hypomethylation and hypermethylation events in medulloblastoma. Br J Cancer 97, 267-274. (Pubitemid 47057473)
88. Anderton, J.A., Lindsey, J., Lusher, M.E., Gilberston, R.J., Bailey, S. et al. (2008) Global analysis of the medulloblastoma epigenome identifi es disease-subgroup-specific inactivation of COL1A2. Neuro Oncol 10, 981-994.
89. Kongkham, P.N., Northcott, P., Ra, Y.S., Nakahara, Y., Mainprize, T.G. et al. (2008) An epigenetic genome-wide screen identifi es SPINT2 a novel tumour suppressor gene in pediatric medulloblastoma. Cancer Res. 68, 9945-9953.
90. Cecchi, F., Rabe, D.C., and Bottaro, D. (2010) Targeting the HGF/MET signalling pathway in cancer. Eur J Cancer 46, 1260-1270.
91. Diede, S.J., Guenthoer, J., Geng, L.N., Mahoney, S.E. and Marotta, M. et al. (2010) DNA methylation of developmental genes in pediatric medulloblastoma identifi ed by denaturation analysis of methylation differences. Proc. Natl. Acad. Sci. 107, 234-239.
92. Pierson, J., Hostager, B., Fan, R. and Vibhakar, R. (2008) Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol 90, 1-7.
93. Ferretti, E., De Smaele, E., Miele, E., Laneve, P., Po, A. et al. (2008) Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO Journal 27, 2616-2627.
94. Ferretti, E., De Smaele, E., Po, A., Di Marcotullio, L., Tosi, E. et al. (2009) MicroRNA profi ling in human medulloblastoma. Int J Cancer 124, 568-577.
95. Northcott, P.A., Fernandez, L.A., Hagan, J.P., Ellison, D.W., Grajkowska, W. et al. (2009) The miR-17/92 Polycistron is Up-Regulated in Sonic Hedgehog Driven Medulloblastoma and Induced by N-Myc in Sonic Hedgehog-Treated Cerebellar Neural Precursors. Cancer Res. 69, 3249-3255.
96. Uziel, T., Karginov, F.V., Xie, S., Parker, J.S., Wang, Y.D. et al. (2009) The mir17-92 cluster collaborates with Sonic Hedgehog pathway in Medulloblastoma. PNAS 106, 2812-2817.
97. Cho, J.Y., Tsherniak, A., Tamayo, P., Santagata, S., Ligon, A. et al. (2010) Integrative Genomic Analysis of Medulloblastoma Identifi es a Molecular Subgroup That Drives Poor Clinical Outcome. J. Clin. Oncol 29, 1424-1430.
98. Northcott, P.A., Nakahara, Y., Wu, X., Feuk, F., Ellison, D.W. et al. (2009) Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nature Genetics 41, 465-472.
99. Teider, N., Scott, D., Neiss, A., Weeraratne, D., Amani, V.M. et al. (2010) Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma. Neuro Oncol 12, 1244-1256.
100. Canettieri, G., Di Marcotullio, M.L., Greco, A., Coni, S., Antonucci, L. et al. (2010) Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli1 acetylation. Nat Cell Biol 12, 132-142.
101. Kilday, J.P., Ruman, R., Dyer, S., Ridley, L., Lowe, J., Coyle, B., and Grundy, R. (2009) Paediatric Ependymoma: Biological Perspectives. Mol. Cancer Res. 7, 27-31.
102. Korshunov, A., Witt, H., Hielscher, T., Benner, A., Remke, M., et al. (2010) Molecular staging of intracranial ependymoma in children and adults. J. Clin. Oncol. 28, 3182-3190.
103. Mack, S.C. and Taylor, M.D. (2009) The genetic and epigenetic basis of ependymoma. Childs Nerv Syst 25, 1195-1201.
104. Johnson, R.A., Wright, K., Poppleton, H., Mohankumar, K.M., Finkelstein, D. et al. (2010) Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 466, 632-636.
105. Hamilton, D.W., Lusher, M.E., Lindsey, J.C., Ellison, D.W., and Clifford, S.C. (2005) Epigenetic inactivation of the RASSF1A tumour suppressor gene in ependymoma. Cancer letters 227, 75-81. (Pubitemid 41033094)
106. von Haken, M.S., White, E.C., Daneshvar-Shyesther, L., Sih, S., Choi, E., et al. (1996) Molecular genetic analysis of chromo- some arm17p and chromosome arm22qDNAsequences in sporadic pediatric ependymomas, Genes Chromosomes Cancer 17, 37-44. (Pubitemid 26327933)
107. Waha, A., Koch, A., Hartmann, W., Mack, H., Schramm, J., et al. (2004) Analysis of HIC-1 methylation and transcription in human ependymomas. Int J Cancer 110, 542-549. (Pubitemid 38658019)
108. Modena, P., Lualdi, E., Facchinetti, F., Veltman, J., Reid, J.F., et al. (2006) Identifi cation of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J. Clin. Oncol 24, 5223-5233. (Pubitemid 46631366)
109. Rousseau, E., Ruchoux, M.M., Scaravilli, F., Chapon, S.F., Vinchon, M. et al. (2003) CDKN2A, CDKN2B and p14ARF are frequently and differentially methylated in ependymal tumours. Neuropathology and Applied Neurobiology 14, 574-583. (Pubitemid 37548352)
110. Koos, B., Peetz-Dienhart, S., Riesmeier, B, Fruhwald, M.C., and Hasselblatt, M. (2010) O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation is signifi -cantly less frequent in ependymal tumours as compared to malignant astrocytic gliomas. Neuropathology and Applied Neurobiology 36, 356-358.
111. Alonso, M.E., Bello, M.J., Gonzalez-Gomez, P., Arjona, D., de Campos, J.M., et al. (2004) Aberrant CpG island methylation of multiple genes in ependymal tumors. J Neuro-oncol 67, 159-165. (Pubitemid 38418264)
112. Sardi, I., Cetica, V., Massimino, M., Buccoliero, A.M., Giunti, L., et al. (2009) Promoter methylation and expression analysis of MGMT in advanced pediatric brain tumors. Oncol Rep 22, 773-779.
113. Xie, H., Wang, M., Bonaldo, M., Veena, R., Stellpfl ug, W., et al. (2010) Epigenomic analysis of Alu repeats in human ependymomas, PNAS 107, 6952-6957.