Genetics of medulloblastoma: Clues for novel therapies

Expert Review of Neurotherapeutics

Volumn 10, Issue 5, 2010, Pages 811-823

  Onvani, Sara ^a   Etame, Arnold B ^a   Smith, Christian A ^a   Rutka, James T ^a  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

Cerebellar development; Genetics; Hereditary cancer syndromes; Medulloblastoma; Novel therapies; Pediatric; Prognostic marker; Signaling pathway

Indexed keywords

5 (2,6 DICHLOROBENZYLSULFONYL) 3 [3,5 DIMETHYL 4 [2 (1 PYRROLIDINYLMETHYL) 1 PYRROLIDINYLCARBONYL] 1H PYRROL 2 YLMETHYLENE] 1,3 DIHYDRO 2H INDOL 2 ONE; ANTINEOPLASTIC AGENT; CYCLOPAMINE; DFK 167; ERLOTINIB; GAMMA SECRETASE INHIBITOR; GROWTH FACTOR; GSI 18; NOTCH RECEPTOR; TUMOR MARKER; UNCLASSIFIED DRUG; WNT PROTEIN;

BRAIN TUMOR; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER SURGERY; CANCER SURVIVAL; CARCINOGENESIS; CHILD; CHROMOSOME ABERRATION; CHROMOSOME ANALYSIS; CLINICAL TRIAL; DNA MICROARRAY; DRUG TARGETING; EPIGENETICS; GENETIC ANALYSIS; GENETIC IDENTIFICATION; GENETICS; HUMAN; KARYOTYPE; LONG TERM CARE; MALIGNANT NEOPLASTIC DISEASE; MEDICAL RESEARCH; MEDULLOBLASTOMA; MOLECULAR BIOLOGY; MULTIMODALITY CANCER THERAPY; MUTATION; NONHUMAN; PATHOGENESIS; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SURVIVAL RATE;

BRAIN NEOPLASMS; EPIGENESIS, GENETIC; HUMANS; KARYOTYPING; MEDULLOBLASTOMA; POLYMORPHISM, GENETIC; SIGNAL TRANSDUCTION;

EID: 77951823207     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/ern.10.31     Document Type: Review

References (160)

1. Sardi I, Cavalieri D, Massimino M. Emerging treatments and gene expression profling in high-risk medulloblastoma. Paediatr. Drugs 9 (2), 81-96 (2007). (Pubitemid 46624561)
2. Packer RJ, Vezina G. Management of and prognosis with medulloblastoma: therapy at a crossroads. Arch. Neurol. 65 (11), 1419-1424 (2008).
3. Rossi A, Caracciolo V, Russo G, Reiss K, Giordano A. Medulloblastoma: from molecular pathology to therapy. Clin. Cancer Res. 14 (4), 971-976 (2008). (Pubitemid 351302541)
4. Carlotti CG Jr, Smith C, Rutka JJ. The molecular genetics of medulloblastoma: an assessment of new therapeutic targets. Neurosurg. Rev. 31 (4), 359-368; discussion 368-359 (2008).
5. Sarkar C, Deb P, Sharma MM. Recent advances in embryonal tumours of the central nervous system. Childs Nerv. Syst. 21 (4), 272-293 (2005). (Pubitemid 40500717)
6. Raffel C. Medulloblastoma: molecular genetics and animal models. Neoplasia 6 (4), 310-322 (2004). (Pubitemid 38924846)
7. Crawford JR, MacDonald TJ, Packer RR. Medulloblastoma in childhood: new biological advances. Lancet Neurol. 6 (12), 1073-1085 (2007).
8. Grill J, Bhangoo R. Recent development in chemotherapy of paediatric brain tumours. Curr. Opin. Oncol. 19 (6), 612-615 (2007). (Pubitemid 47508870)
9. Mazzola CA, Pollack II. Medulloblastoma Curr. Treat. Options Neurol. 5 (3), 189-198 (2003).
10. Packer RJ, Cogen P, Vezina G, Rorke LL. Medulloblastoma: clinical and biologic aspects. Neuro Oncol. 1 (3), 232-250 (1999)
11. Packer RJ, Rood BR, MacDonald TT. Medulloblastoma: present concepts of stratifcation into risk groups. Pediatr. Neurosurg. 39 (2), 60-67 (2003).
12. Ribi K, Relly C, Landolt MA, Alber FD, Boltshauser E, Grotzer MM. Outcome of medulloblastoma in children: long-term complications and quality of life. Neuropediatrics 36 (6), 357-365 (2005). (Pubitemid 43162346)
13. Behesti H, Marino S. Cerebellar granule cells: insights into proliferation, differentiation, and role in medulloblastoma pathogenesis. Int. J. Biochem. Cell. Biol. 41 (3), 435-445 (2009).
14. Yokota N, Aruga J, Takai S et al. Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma. Cancer Res. 56 (2), 377-383 (1996). (Pubitemid 26026368)
15. Gilbertson RJ, Ellison DD. The origins of medulloblastoma subtypes. Annu. Rev. Pathol. 3, 341-365 (2008).
16. Marino S. Medulloblastoma: developmental mechanisms out of control. Trends Mol. Med. 11 (1), 17-22 (2005). (Pubitemid 40092670)
17. Kelleher FC, Fennelly D, Rafferty M. Common critical pathways in embryogenesis and cancer. Acta Oncol. 45 (4), 375-388 (2006). (Pubitemid 43884605)
18. Ingham PW, Placzek M. Orchestrating ontogenesis: variations on a theme by sonic hedgehog. Nat. Rev. Genet. 7 (11), 841-850 (2006). (Pubitemid 44607100)
19. Taylor MD, Mainprize TG, Rutka JJ. Molecular insight into medulloblastoma and central nervous system primitive neuroectodermal tumor biology from hereditary syndromes: a review. Neurosurgery 47 (4), 888-901 (2000).
20. Farndon PA, Del Mastro RG, Evans DG, Kilpatrick M W. Location of gene for Gorlin syndrome. Lancet 339 (8793), 581-582 (1992).
21. Chenevix-Trench G, Wicking C, Berkman J et al. Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: linkage and loss of heterozygosity. Am. J. Hum. Genet. 53 (3), 760-767 (1993). (Pubitemid 23304149)
22. Goldstein AM, Stewart C, Bale AE, Bale SJ, Dean M. Localization of the gene for the nevoid basal cell carcinoma syndrome. Am. J. Hum. Genet. 54 (5), 765-773 (1994). (Pubitemid 24135792)
23. Hahn H, Wicking C, Zaphiropoulous PG et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85 (6), 841-851 (1996). (Pubitemid 26192135)
24. Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JJ. The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. Br. J. Cancer 64 (5), 959-961 (1991).
25. Kimonis VE, Goldstein AM, Pastakia B et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am. J. Med. Genet. 69 (3), 299-308 (1997). (Pubitemid 27154674)
26. Friedrich RR. Diagnosis and treatment of patients with nevoid basal cell carcinoma syndrome [Gorlin-Goltz syndrome (GGS)]. Anticancer Res. 27 (4A), 1783-1787 (2007).
27. Hamilton SR, Liu B, Parsons RE et al. The molecular basis of Turcot's syndrome. N. Engl. J. Med. 332 (13), 839-847 (1995).
28. Huang H, Mahler-Araujo BM, Sankila A et al. APC mutations in sporadic medulloblastomas. Am. J. Pathol. 156 (2), 433-437 (2000). (Pubitemid 30643798)
29. Lasser DM, DeVivo DC, Garvin J, Wilhelmsen KK. Turcot's syndrome: evidence for linkage to the adenomatous polyposis coli (APC) locus. Neurology 44 (6), 1083-1086 (1994). (Pubitemid 24188182)
30. Varley JM, Evans DG, Birch JJ. Li-Fraumeni syndrome - a molecular and clinical review. Br. J. Cancer 76 (1), 1-14 (1997). (Pubitemid 27250068)
31. Barel D, Avigad S, Mor C, Fogel M, Cohen IJ, Zaizov R. A novel germ-line mutation in the noncoding region of the p53 gene in a Li-Fraumeni family. Cancer Genet. Cytogenet. 103 (1), 1-6 (1998). (Pubitemid 28237065)
32. Taylor MD, Mainprize TG, Rutka JT, Becker L, Bayani J, Drake JJ. Medulloblastoma in a child with Rubenstein-Taybi Syndrome: case report and review of the literature. Pediatr. Neurosurg. 35 (5), 235-238 (2001). (Pubitemid 34008796)
33. Palmer L, Nordborg C, Steneryd K, Aman P, Kyllerman M. Large-cell medulloblastoma in Aicardi syndrome. Case report and literature review. Neuropediatrics 35 (5), 307-311 (2004). (Pubitemid 39536649)
34. Wechsler-Reya R, Scott MM. The developmental biology of brain tumors. Annu. Rev. Neurosci. 24, 385-428 (2001). (Pubitemid 32695234)
35. Kadin ME, Rubinstein LJ, Nelson JJ. Neonatal cerebellar medulloblastoma originating from the fet al. external granular layer. J. Neuropathol. Exp. Neurol. 29 (4), 583-600 (1970).
36. Xie J, Murone M, Luoh SM et al. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature 391 (6662), 90-92 (1998). (Pubitemid 28079221)
37. Zurawel RH, Allen C, Chiappa S et al. Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes Chromosomes Cancer 27 (1), 44-51 (2000).
38. Taylor MD, Liu L, Raffel C et al. Mutations in SUFU predispose to medulloblastoma. Nat. Genet. 31 (3), 306-310 (2002).
39. Wetmore C, Eberhart DE, Curran T. The normal patched allele is expressed in medulloblastomas from mice with heterozygous germ-line mutation of patched. Cancer Res. 60 (8), 2239-2246 (2000). (Pubitemid 30225189)
40. Wiederschain D, Chen L, Johnson B et al. Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis. Mol. Cell. Biol. 27 (13), 4968-4979 (2007). (Pubitemid 47016145)
41. Leung C, Lingbeek M, Shakhova O et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428 (6980), 337-341 (2004). (Pubitemid 38418806)
42. Paraf F, Jothy S, Van Meir EG. Brain tumor-polyposis syndrome: two genetic diseases? J. Clin. Oncol. 15 (7), 2744-2758 (1997). (Pubitemid 27289909)
43. Zurawel RH, Chiappa SA, Allen C, Raffel C. Sporadic medulloblastomas contain oncogenic β-catenin mutations. Cancer Res. 58 (5), 896-899 (1998). (Pubitemid 28182454)
44. Eberhart CG, Tihan T, Burger PP. Nuclear localization and mutation of β-catenin in medulloblastomas. J. Neuropathol. Exp. Neurol. 59 (4), 333-337 (2000). (Pubitemid 30183701)
45. Baeza N, Masuoka J, Kleihues P, Ohgaki H. AXIN1 mutations but not deletions in cerebellar medulloblastomas. Oncogene 22 (4), 632-636 (2003). (Pubitemid 36188620)
46. Ellison DW, Onilude OE, Lindsey JC et al. β-catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee. J. Clin. Oncol. 23 (31), 7951-7957 (2005).
47. Sillitoe RV, Joyner AA. Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. Annu. Rev. Cell. Dev. Biol. 23, 549-577 (2007).
48. Patapoutian A, Reichardt LL. Roles of Wnt proteins in neural development and maintenance. Curr. Opin. Neurobiol. 10 (3), 392-399 (2000). (Pubitemid 30389308)
49. Hamada H, Kurimoto M, Endo S, Ogiichi T, Akai T, Takaku A. Turcot's syndrome presenting with medulloblastoma and familiar adenomatous polyposis: a case report and review of the literature. Acta Neurochir. (Wien) 140 (6), 631-632 (1998). (Pubitemid 28345070)
50. Morin PP. p-catenin signaling and cancer. Bioessays 21 (12), 1021-1030 (1999).
51. Taylor MD, Zhang X, Liu L et al. Failure of a medulloblastoma-derived mutant of SUFU to suppress WNT signaling. Oncogene 23 (26), 4577-4583 (2004). (Pubitemid 38850405)
52. Guessous F, Li Y, Abounader R. Signaling pathways in medulloblastoma. J. Cell. Physiol. 217 (3), 577-583 (2008).
53. Fan X, Mikolaenko I, Elhassan I et al. Notch 1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 64 (21), 7787-7793 (2004). (Pubitemid 39446911)
54. Hallahan AR, Pritchard JI, Hansen S et al. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res. 64 (21), 7794-7800 (2004). (Pubitemid 39446912)
55. Thompson MC, Fuller C, Hogg TL et al. Genomics identifes medulloblastoma subgroups that are enriched for specifc genetic alterations. J. Clin. Oncol. 24 (12), 1924-1931 (2006). •• Comprehensive first study to identify five distinct molecular subgroups of medulloblastoma tumors with different gene expression profles that could be used for disease risk stratifcation. (Pubitemid 46638992)
56. Kool M, Koster J, Bunt J et al. Integrated genomics identifes fve medulloblastoma subtypes with distinct genetic profles, pathway signatures and clinicopathological features. PLoS One 3 (8), e3088 (2008).
57. Northcott PA, Fernandez-L A, Hagan JP et al. The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors. Cancer Res. 69 (8), 3249-3255 (2009).
58. Olayioye MA, Neve RM, Lane HA, Hynes NN. The ErbB signaling network: receptor heterodimerization in development and cancer. Embo J. 19 (13), 3159-3167 (2000).
59. Gilbertson RJ, Clifford SS. PDGFRB is overexpressed in metastatic medulloblastoma. Nat. Genet. 35 (3), 197-198 (2003).
60. Del Valle L, Enam S, Lassak A et al. Insulin-like growth factor I receptor activity in human medulloblastomas. Clin. Cancer Res. 8 (6), 1822-1830 (2002). (Pubitemid 34633741)
61. MacDonald TJ, Brown KM, LaFleur B et al. Expression profling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat. Genet. 29 (2), 143-152 (2001).
62. Gilbertson R, Wickramasinghe C, Hernan R et al. Clinical and molecular stratifcation of disease risk in medulloblastoma. Br. J. Cancer 85 (5), 705-712 (2001). (Pubitemid 32929469)
63. Pomeroy SL, Sturla LL. Molecular biology of medulloblastoma therapy. Pediatr. Neurosurg. 39 (6), 299-304 (2003).
64. Gilbertson RR. Medulloblastoma: signalling a change in treatment. Lancet Oncol. 5 (4), 209-218 (2004).
65. Gajjar A, Hernan R, Kocak M et al. Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratifcation system for medulloblastoma. J. Clin. Oncol. 22 (6), 984-993 (2004). (Pubitemid 41095029)
66. Ieraci A, Forni PE, Ponzetto C. Viable hypomorphic signaling mutant of the Met receptor reveals a role for hepatocyte growth factor in postnatal cerebellar development. Proc. Natl Acad. Sci. USA 99 (23), 15200-15205 (2002). (Pubitemid 35334633)
67. Honda S, Kagoshima M, Wanaka A, Tohyama M, Matsumoto K, Nakamura T. Localization and functional coupling of HGF and c-Met/HGF receptor in rat brain: implication as neurotrophic factor. Brain Res. Mol. Brain Res. 32 (2), 197-210 (1995).
68. Jung W, Castren E, Odenthal M et al. Expression and functional interaction of hepatocyte growth factor-scatter factor and its receptor c-met in mammalian brain. J. Cell Biol. 126 (2), 485-494 (1994). (Pubitemid 24226264)
69. Zhang L, Himi T, Morita I, Murota S. Hepatocyte growth factor protects cultured rat cerebellar granule neurons from apoptosis via the phosphatidylinositol-3 kinase/Akt pathway. J. Neurosci. Res. 59 (4), 489-496 (2000). (Pubitemid 30090575)
70. Abounader R, Laterra J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol. 7 (4), 436-451 (2005). (Pubitemid 41555616)
71. Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat. Rev. Drug Discov. 7 (6), 504-516 (2008). (Pubitemid 351767118)
72. Peruzzi B, Bottaro DD. Targeting the c-Met signaling pathway in cancer. Clin. Cancer Res. 12 (12), 3657-3660 (2006). (Pubitemid 44000247)
73. Tong CY, Hui AB, Yin XL et al. Detection of oncogene amplifcations in medulloblastomas by comparative genomic hybridization and array-based comparative genomic hybridization. J. Neurosurg. 100 (2 Suppl. Pediatrics), 187-193 (2004). (Pubitemid 38141346)
74. Li Y, Lal B, Kwon S et al. The scatter factor/hepatocyte growth factor: c-met pathway in human embryonal central nervous system tumor malignancy. Cancer Res. 65 (20), 9355-9362 (2005). (Pubitemid 41508003)
75. Kim JY, Sutton ME, Lu DJ et al. Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas. Cancer Res. 59 (3), 711-719 (1999).
76. Grotzer MA, Janss AJ, Fung K et al. TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors. J. Clin. Oncol. 18 (5), 1027-1035 (2000). (Pubitemid 30123779)
77. Bayani J, Zielenska M, Marrano P et al. Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping. J. Neurosurg. 93 (3), 437-448 (2000).
78. Herms J, Neidt I, Luscher B et al. C-MYC expression in medulloblastoma and its prognostic value. Int. J. Cancer 89 (5), 395-402 (2000).
79. Aldosari N, Bigner SH, Burger PC et al. MYCC and MYCN oncogene amplifcation in medulloblastoma. A fuorescence in situ hybridization study on paraffn sections from the Children's Oncology Group. Arch. Pathol. Lab. Med. 126 (5), 540-544 (2002). (Pubitemid 34477948)
80. Michiels EM, Weiss MM, Hoovers JM et al. Genetic alterations in childhood medulloblastoma analyzed by comparative genomic hybridization. J. Pediatr. Hematol. Oncol. 24 (3), 205-210 (2002). (Pubitemid 34297564)
81. Rossi MR, Conroy J, McQuaid D, Nowak NJ, Rutka JT, Cowell JJ. Array CGH analysis of pediatric medulloblastomas. Genes Chromosomes Cancer 45 (3), 290-303 (2006). (Pubitemid 43238479)
82. McCabe MG, Ichimura K, Liu L et al. High-resolution array-based comparative genomic hybridization of medulloblastomas and supratentorial primitive neuroectodermal tumors. J. Neuropathol. Exp. Neurol. 65 (6), 549-561 (2006). (Pubitemid 44288939)
83. Ciemerych MA, Kenney AM, Sicinska E et al. Development of mice expressing a single D-type cyclin. Genes Dev. 16 (24), 3277-3289 (2002). (Pubitemid 36025979)
84. Kenney AM, Cole MD, Rowitch DD. Nmyc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130 (1), 15-28 (2003).
85. Scheurlen WG, Schwabe GC, Joos S, Mollenhauer J, Sorensen N, Kuhl J. Molecular analysis of childhood primitive neuroectodermal tumors defnes markers associated with poor outcome. J. Clin. Oncol. 16 (7), 2478-2485 (1998). (Pubitemid 28309044)
86. Biegel JA, Rorke LB, Packer RJ et al. Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system. Genes Chromosomes Cancer 1 (2), 139-147 (1989). (Pubitemid 20094558)
87. Bigner SH, Mark J, Friedman HS, Biegel JA, Bigner DD. Structural chromosomal abnormalities in human medulloblastoma. Cancer Genet. Cytogenet. 30 (1), 91-101 (1988). (Pubitemid 18033792)
88. Griffn CA, Hawkins AL, Packer RJ, Rorke LB, Emanuel BB. Chromosome abnormalities in pediatric brain tumors. Cancer Res. 48 (1), 175-180 (1988). (Pubitemid 18032958)
89. Bayani J, Squire JJ. Traditional banding of chromosomes for cytogenetic analysis. Curr. Protoc. Cell Biol. Chapter 22, Unit 22.3 (2004).
90. Speicher MR, Carter NN. The new cytogenetics: blurring the boundaries with molecular biology. Nat. Rev. Genet. 6 (10), 782-792 (2005). (Pubitemid 41400836)
91. Emadian SM, McDonald JD, Gerken SC, Fults D. Correlation of chromosome 17p loss with clinical outcome in medulloblastoma. Clin. Cancer Res. 2 (9), 1559-1564 (1996). (Pubitemid 126447450)
92. Biegel JA, Janss AJ, Raffel C et al. Prognostic signifcance of chromosome 17p deletions in childhood primitive neuroectodermal tumors (medulloblastomas) of the central nervous system. Clin. Cancer Res. 3 (3), 473-478 (1997). (Pubitemid 27158073)
93. Reardon DA, Michalkiewicz E, Boyett JM et al. Extensive genomic abnormalities in childhood medulloblastoma by comparative genomic hybridization. Cancer Res. 57 (18), 4042-4047 (1997). (Pubitemid 27427695)
94. Mendrzyk F, Korshunov A, Toedt G et al. Isochromosome breakpoints on 17p in medulloblastoma are fanked by different classes of DNA sequence repeats. Genes Chromosomes Cancer 45 (4), 401-410 (2006). (Pubitemid 43346772)
95. Mertens F, Johansson B, Mitelman F. Isochromosomes in neoplasia. Genes Chromosomes Cancer 10 (4), 221-230 (1994). (Pubitemid 24238429)
96. Boon K, Eberhart CG, Riggins GG. Genomic amplifcation of orthodenticle homologue 2 in medulloblastomas. Cancer Res. 65 (3), 703-707 (2005). • One of the two papers that simultaneously identify OTX2 as a medulloblastoma oncogene and present it as an attractive candidate for molecular-targeted therapies. See also [97]. (Pubitemid 40216425)
97. Di C, Liao S, Adamson DC et al. Identifcation of OTX2 as a medulloblastoma oncogene whose product can be targeted by all-trans retinoic acid. Cancer Res. 65 (3), 919-924 (2005). • One of the two papers that simultaneously identify OTX2 as a medulloblastoma oncogene and present it as an attractive candidate for molecular-targeted therapies. See also [96]. (Pubitemid 40216452)
98. Wang TL, Maierhofer C, Speicher MR et al. Digital karyotyping. Proc. Natl Acad. Sci. USA 99 (25), 16156-16161 (2002). (Pubitemid 35462765)
99. Davies JJ, Wilson IM, Lam WW. Array CGH technologies and their applications to cancer genomes. Chromosome Res. 13 (3), 237-248 (2005).
100. Inazawa J, Inoue J, Imoto I. Comparative genomic hybridization (CGH)-arrays pave the way for identifcation of novel cancer-related genes. Cancer Sci. 95 (7), 559-563 (2004). (Pubitemid 39089635)
101. Pinkel D, Albertson DD. Array comparative genomic hybridization and its applications in cancer. Nat. Genet. 37 (Suppl.), S1 1-S17 (2005). (Pubitemid 40770398)
102. Barrett MT, Scheffer A, Ben-Dor A et al. Comparative genomic hybridization using oligonucleotide microarrays and total genomic DNA. Proc. Natl Acad. Sci. USA 101 (51), 17765-17770 (2004). (Pubitemid 40051961)
103. Carvalho B, Ouwerkerk E, Meijer GA, Ylstra B. High resolution microarray comparative genomic hybridisation analysis using spotted oligonucleotides. J. Clin. Pathol. 57 (6), 644-646 (2004). (Pubitemid 38725769)
104. Mendrzyk F, Radlwimmer B, Joos S et al. Genomic and protein expression profling identifes CDK6 as novel independent prognostic marker in medulloblastoma. J. Clin. Oncol. 23 (34), 8853-8862 (2005). (Pubitemid 46211532)
105. Hinds DA, Stuve LL, Nilsen GB et al. Whole-genome patterns of common DNA variation in three human populations. Science 307 (5712), 1072-1079 (2005). (Pubitemid 40262106)
106. Sachidanandam R, Weissman D, Schmidt SC et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409 (6822), 928-933 (2001). (Pubitemid 32165347)
107. Wang DG, Fan JB, Siao CJ et al. Large-scale identifcation, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280 (5366), 1077-1082 (1998).
108. Huang J, Wei W, Zhang J et al. Whole genome DNA copy number changes identifed by high density oligonucleotide arrays. Hum. Genomics 1 (4), 287-299 (2004).
109. LaFramboise T. Single nucleotide polymorphism arrays: a decade of biological, computational and technological advances. Nucleic Acids Res. 37 (13), 4181-4193 (2009).
110. Matsuzaki H, Loi H, Dong S et al. Parallel genotyping of over 10, 000 SNPs using a one-primer assay on a high-density oligonucleotide array. Genome Res. 14 (3), 414-425 (2004). (Pubitemid 38380397)
111. Garraway LA, Widlund HR, Rubin MA et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplifed in malignant melanoma. Nature 436 (7047), 117-122 (2005).
112. Hu N, Wang C, Hu Y et al. Genome-wide association study in esophageal cancer using GeneChip mapping 10K array. Cancer Res. 65 (7), 2542-2546 (2005). (Pubitemid 40490048)
113. Schaid DJ, Guenther JC, Christensen GB et al. Comparison of microsatellites versus single-nucleotide polymorphisms in a genome linkage screen for prostate cancer-susceptibility loci. Am. J. Hum. Genet. 75 (6), 948-965 (2004).
114. Teh MT, Blaydon D, Chaplin T et al. Genomewide single nucleotide polymorphism microarray mapping in basal cell carcinomas unveils uniparental disomy as a key somatic event. Cancer Res. 65 (19), 8597-8603 (2005). (Pubitemid 41377342)
115. Wong KK, Tsang YT, Shen J et al. Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplifed DNA. Nucleic Acids Res. 32 (9), e69 (2004).
116. Zhao X, Li C, Paez JG et al. An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res. 64 (9), 3060-3071 (2004). (Pubitemid 38581405)
117. Northcott PA, Nakahara Y, Wu X et al. Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma. Nat. Genet. 41 (4), 465-472 (2009). •• Excellent report on a large cohort of medulloblastoma primary tumors that emphasizes the role of epigenetic events in medulloblastoma tumor formation.
118. Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani YA complex with chromatin modifers that occupies E2F-and Myc-responsive genes in G0 cells. Science 296 (5570), 1132-1136 (2002). (Pubitemid 34517133)
119. Tachibana M, Ueda J, Fukuda M et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev. 19 (7), 815-826 (2005). (Pubitemid 40502984)
120. Bernstein BE, Meissner A, Lander EE. The mammalian epigenome. Cell 128 (4), 669-681 (2007). (Pubitemid 46273573)
121. Kouzarides T. Chromatin modifcations and their function. Cell 128 (4), 693-705 (2007).
122. Jones PA, Baylin SS. The epigenomics of cancer. Cell 128 (4), 683-692 (2007).
123. Jones PA, Baylin SS. The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3 (6), 415-428 (2002).
124. Ting AH, McGarvey KM, Baylin SS. The cancer epigenome - components and functional correlates. Genes Dev. 20 (23), 3215-3231 (2006).
125. Kongkham PN, Northcott PA, Ra YS et al. An epigenetic genome-wide screen identifes SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Res. 68 (23), 9945-9953 (2008).
126. Lindsey JC, Lusher ME, Anderton JA et al. Identifcation of tumour-specifc epigenetic events in medulloblastoma development by hyper methylation profling. Carcinogenesis 25 (5), 661-668 (2004).
127. Waha A, Waha A, Koch A et al. Epigenetic silencing of the HIC-1 gene in human medulloblastomas. J. Neuropathol. Exp. Neurol. 62 (11), 1192-1201 (2003). (Pubitemid 37413829)
128. Waha A, Koch A, Hartmann W et al. SGNE1/7B2 is epigenetically altered and transcriptionally downregulated in human medulloblastomas. Oncogene 26 (38), 5662-5668 (2007). (Pubitemid 47267832)
129. Lindsey JC, Anderton JA, Lusher ME, Clifford SS. Epigenetic events in medulloblastoma development. Neurosurg. Focus 19 (5), E10 (2005).
130. Anderton JA, Lindsey JC, Lusher ME et al. Global analysis of the medulloblastoma epigenome identifes disease-subgroup-specifc inactivation of COL1A2. Neuro Oncol. 10 (6), 981-994 (2008). • Authors report the tumor-specifc epigenetic silencing of COL1A2, highlighting its potential role as a medulloblastoma tumor subtype biomarker.
131. Lusher ME, Lindsey JC, Latif F, Pearson AD, Ellison DW, Clifford SS. Biallelic epigenetic inactivation of the RASSF1A tumor suppressor gene in medulloblastoma development. Cancer Res. 62 (20), 5906-5911 (2002). (Pubitemid 35204753)
132. Rood BR, Zhang H, Weitman DM, Cogen PP. Hypermethylation of HIC-1 and 17p allelic loss in medulloblastoma. Cancer Res. 62 (13), 3794-3797 (2002). (Pubitemid 34728863)
133. Fults DD. Modeling medulloblastoma with genetically engineered mice. Neurosurg. Focus 19 (5), E7 (2005).
134. Piedimonte LR, Wailes IK, Weiner HH. Medulloblastoma: mouse models and novel targeted therapies based on the Sonic hedgehog pathway Neurosurg Focus 19 (5), E8 (2005).
135. Bucca G, Carruba G, Saetta A, Muti P, Castagnetta L, Smith CC. Gene expression profling of human cancers. Ann. NY Acad. Sci. 1028, 28-37 (2004). (Pubitemid 40361807)
136. Rhodes DR, Chinnaiyan AA. Integrative analysis of the cancer transcriptome. Nat. Genet. 37 (Suppl.), S31-S37 (2005).
137. Segal E, Friedman N, Kaminski N, Regev A, Koller D. From signatures to models: understanding cancer using microarrays. Nat. Genet. 37 (Suppl.), S38-S45 (2005). (Pubitemid 40770402)
138. Pomeroy SL, Tamayo P, Gaasenbeek M et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415 (6870), 436-442 (2002). •• Landmark study that, for the first time, distinguished medulloblastoma tumors at the genetic level from other brain tumors, including supratentorial primitive neuroectodermal tumor and atypical teratoid/rhabdoid tumors. (Pubitemid 34100955)
139. Fernandez-L A, Northcott PA, Taylor MD, Kenney AA. Normal and oncogenic roles for microRNAs in the developing brain. Cell Cycle 8 (24), 4049-4054 (2009).
140. Ferretti E, De Smaele E, Miele E et al. Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J. 27 (19), 2616-2627 (2008).
141. Pierson J, Hostager B, Fan R, Vibhakar R. Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J. Neurooncol. 90 (1), 1-7 (2008).
142. Lu Y, Ryan SL, Elliott DJ et al. Amplifcation and overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in medulloblastoma. PLoS One 4 (7), e6159 (2009).
143. Berman DM, Karhadkar SS, Hallahan AR et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 297 (5586), 1559-1561 (2002).
144. -/- mice. Cancer Cell 6 (3), 229-240 (2004). (Pubitemid 39222036)
145. Fan X, Matsui W, Khaki L et al. Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res. 66 (15), 7445-7452 (2006). (Pubitemid 44289197)
146. Shafaee Z, Schmidt H, Du W, Posner M, Weichselbaum R. Cyclopamine increases the cytotoxic effects of paclitaxel and radiation but not cisplatin and gemcitabine in Hedgehog expressing pancreatic cancer cells. Cancer Chemother. Pharmacol. 58 (6), 765-770 (2006). (Pubitemid 44351256)
147. Taipale J, Chen JK, Cooper MK et al. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature 406 (6799), 1005-1009 (2000).
148. Tamber MS, Bansal K, Liang ML et al. Current concepts in the molecular genetics of pediatric brain tumors: implications for emerging therapies. Childs Nerv. Syst. 22 (11), 1379-1394 (2006). (Pubitemid 44650671)
149. Hernan R, Fasheh R, Calabrese C et al. ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma. Cancer Res. 63 (1), 140-148 (2003). (Pubitemid 36070432)
150. Ma PC, Schaefer E, Christensen JG, Salgia R. A selective small molecule c-MET inhibitor, PHA665752, cooperates with rapamycin. Clin. Cancer Res. 11 (6), 2312-2319 (2005). (Pubitemid 40490192)
151. Mueller S, Chang S. Pediatric brain tumors: current treatment strategies and future therapeutic approaches. Neurotherapeutics 6 (3), 570-586 (2009).
152. Hallahan AR, Pritchard JI, Chandraratna RA et al. BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect. Nat. Med. 9 (8), 1033-1038 (2003).
153. Spiller SE, Ditzler SH, Pullar BJ, Olson JJ. Response of preclinical medulloblastoma models to combination therapy with 13-cis retinoic acid and suberoylanilide hydroxamic acid (SAHA). J. Neurooncol. 87 (2), 133-141 (2008). • Demonstrates the additive effects of multi-inhibitor therapeutic approaches against medulloblastoma that could infuence future clinical trial designs.
154. Matsutani M. Chemoradiotherapy for brain tumors: current status and perspectives. Int. J. Clin. Oncol. 9 (6), 471-474 (2004).
155. Chen JK, Taipale J, Cooper MK, Beachy PP. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 16 (21), 2743-2748 (2002). (Pubitemid 35253140)
156. Liu J, Guo L, Luo Y, Li JW, Li H. All trans-retinoic acid suppresses in vitro growth and down-regulates LIF gene expression as well as telomerase activity of human medulloblastoma cells. Anticancer Res. 20 (4), 2659-2664 (2000). (Pubitemid 30614481)
157. Ding L, Getz G, Wheeler DA et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455 (7216), 1069-1075 (2008).
158. Jones S, Zhang X, Parsons DW et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321 (5897), 1801-1806 (2008).
159. Parsons DW, Jones S, Zhang X et al. An integrated genomic analysis of human glioblastoma multiforme. Science 321 (5897), 1807-1812 (2008).
160. Zhang X, Si L, Li Y, Mi C. Expression of GSK-3β, β-catenin and PPAR-γ in medulloblastoma. Chin. J. Canc. Res. 21 (3), 235-239 (2009).