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Sarcoma
Volume 2011, Article ID 362173, 10 pages
http://dx.doi.org/10.1155/2011/362173
Review Article

Copy Number Alterations and Methylation in Ewing's Sarcoma

1Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
2Department of Orthopaedics, Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
3Center for Children's Cancer Research (C3R), Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Salt Lake City, UT 84112, USA
4Division of Pediatric Hematology/Oncology, Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Salt Lake City, UT 84112, USA

Received 15 September 2010; Accepted 3 January 2011

Academic Editor: Peter Houghton

Copyright © 2011 Mona S. Jahromi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. Granowetter, R. Womer, M. Devidas et al., “Dose-intensified compared with standard chemotherapy for nonmetastatic ewing sarcoma family of tumors: a children's oncology group study,” Journal of Clinical Oncology, vol. 27, no. 15, pp. 2536–2541, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. H. E. Grier, M. D. Krailo, N. J. Tarbell et al., “Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone,” New England Journal of Medicine, vol. 348, no. 8, pp. 694–701, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. L. M. Barker, T. W. Pendergrass, J. E. Sanders, and D. S. Hawkins, “Survival after recurrence of Ewing's sarcoma family of tumors,” Journal of Clinical Oncology, vol. 23, no. 19, pp. 4354–4362, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Rodriguez-Galindo, C. A. Billups, L. E. Kun et al., “Survival after recurrence of ewing tumors: the St. Jude children's research hospital experience, 1979–1999,” Cancer, vol. 94, no. 2, pp. 561–569, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. A. G. Shankar, S. Ashley, A. W. Craft, and C. R. Pinkerton, “Outcome after relapse in an unselected cohort of children and adolescents with Ewing sarcoma,” Medical and Pediatric Oncology, vol. 40, no. 3, pp. 141–147, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. S. G. DuBois, M. D. Krailo, S. L. Lessnick et al., “Phase II study of intermediate-dose cytarabine in patients with relapsed or refractory ewing sarcoma: a report from the children's oncology group,” Pediatric Blood and Cancer, vol. 52, no. 3, pp. 324–327, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. J. S. Miser, M. D. Krailo, N. J. Tarbell et al., “Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide—a children's cancer group and pediatric oncology group study,” Journal of Clinical Oncology, vol. 22, no. 14, pp. 2873–2876, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. S. A. Burchill, “Ewing's sarcoma: diagnostic, prognostic, and therapeutic implications of molecular abnormalities,” Journal of Clinical Pathology, vol. 56, no. 2, pp. 96–102, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. C. R. Walkley, R. Qudsi, V. G. Sankaran et al., “Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease,” Genes and Development, vol. 22, no. 12, pp. 1662–1676, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Riggi, L. Cironi, P. Provero et al., “Development of Ewing's sarcoma from primary bone marrow-derived mesenchymal progenitor cells,” Cancer Research, vol. 65, no. 24, pp. 11459–11468, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. N. Riggi, M. L. Suvà, D. Suvà et al., “EWS-FLI-1 expression triggers a ewing's sarcoma initiation program in primary human mesenchymal stem cells,” Cancer Research, vol. 68, no. 7, pp. 2176–2185, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. F. Tirode, K. Laud-Duval, A. Prieur, B. Delorme, P. Charbord, and O. Delattre, “Mesenchymal stem cell features of Ewing tumors,” Cancer Cell, vol. 11, no. 5, pp. 421–429, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. F. Baliko, T. Bright, R. Poon, B. Cohen, S. E. Egan, and B. A. Alman, “Inhibition of notch signaling induces neural differentiation in Ewing sarcoma,” American Journal of Pathology, vol. 170, no. 5, pp. 1686–1694, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. A. O. Cavazzana, J. S. Miser, J. Jefferson, and T. J. Triche, “Experimental evidence for a neural origin of Ewing's sarcoma of bone,” American Journal of Pathology, vol. 127, no. 3, pp. 507–518, 1987. View at Google Scholar · View at Scopus
  15. A. Franchi, G. Pasquinelli, G. Cenacchi et al., “Immunohistochemical and ultrastructural investigation of neural differentiation in Ewing sarcoma/PNET of bone and soft tissues,” Ultrastructural Pathology, vol. 25, no. 3, pp. 219–225, 2001. View at Google Scholar · View at Scopus
  16. M. Lipinski, K. Braham, and I. Philip, “Neuroectoderm-associated antigens on Ewing's sarcoma cell lines,” Cancer Research, vol. 47, no. 1, pp. 183–187, 1987. View at Google Scholar · View at Scopus
  17. M. S. Staege, C. Hutter, I. Neumann et al., “DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets,” Cancer Research, vol. 64, no. 22, pp. 8213–8221, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. O. Delattre, J. Zucman, B. Plougastel et al., “Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours,” Nature, vol. 359, no. 6391, pp. 162–165, 1992. View at Publisher · View at Google Scholar · View at Scopus
  19. I. S. Jeon, J. N. Davis, B. S. Braun et al., “A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1,” Oncogene, vol. 10, no. 6, pp. 1229–1234, 1995. View at Google Scholar · View at Scopus
  20. M. Peter, J. Couturier, H. Pacquement et al., “A new member of the ETS family fused to EWS in Ewing tumors,” Oncogene, vol. 14, no. 10, pp. 1159–1164, 1997. View at Google Scholar · View at Scopus
  21. P. H. B. Sorensen, S. L. Lessnick, D. Lopez-Terrada, X. F. Liu, T. J. Triche, and C. T. Denny, “A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG,” Nature Genetics, vol. 6, no. 2, pp. 146–151, 1994. View at Publisher · View at Google Scholar · View at Scopus
  22. C. Turc-Carel, A. Aurias, F. Mugneret et al., “Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases and remarkable consistency of t(11;22)(q24;q12),” Cancer Genetics and Cytogenetics, vol. 32, no. 2, pp. 229–238, 1988. View at Google Scholar · View at Scopus
  23. S. L. Lessnick, B. S. Braun, C. T. Denny, and W. A. May, “Multiple domains mediate transformation by the Ewing's sarcoma EWS/FLI-1 fusion gene,” Oncogene, vol. 10, no. 3, pp. 423–431, 1995. View at Google Scholar · View at Scopus
  24. B. S. Braun, R. Frieden, S. L. Lessnick, W. A. May, and C. T. Denny, “Identification of target genes for the Ewing's sarcoma EWS/FLI fusion protein by representational difference analysis,” Molecular and Cellular Biology, vol. 15, no. 8, pp. 4623–4630, 1995. View at Google Scholar · View at Scopus
  25. M. Kinsey, R. Smith, and S. L. Lessnick, “NR0B1 is required for the oncogenic phenotype mediated by EWS/FLI in Ewing's sarcoma,” Molecular Cancer Research, vol. 4, no. 11, pp. 851–859, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. W. Luo, K. Gangwal, S. Sankar, K. M. Boucher, D. Thomas, and S. L. Lessnick, “GSTM4 is a microsatellite-containing EWS/FLI target involved in Ewing's sarcoma oncogenesis and therapeutic resistance,” Oncogene, vol. 28, no. 46, pp. 4126–4132, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. L. A. Owen and S. L. Lessnick, “Identification of target genes in their native cellular context: an analysis of EWS/FLI in Ewing's sarcoma,” Cell Cycle, vol. 5, no. 18, pp. 2049–2053, 2006. View at Google Scholar · View at Scopus
  28. G. Potikyan, R. O. V. Savene, J. M. Gaulden et al., “EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins,” Cancer Research, vol. 67, no. 14, pp. 6675–6684, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Smith, L. A. Owen, D. J. Trem et al., “Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma,” Cancer Cell, vol. 9, no. 5, pp. 405–416, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. J. P. Zwerner and W. A. May, “PDGC-C is an EWS/FLI induced transforming growth factor in Ewing family tumors,” Oncogene, vol. 20, no. 5, pp. 626–633, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. E. C. Toomey, J. D. Schiffman, and S. L. Lessnick, “Recent advances in the molecular pathogenesis of Ewing's sarcoma,” Oncogene, vol. 29, no. 32, pp. 4504–4516, 2010. View at Publisher · View at Google Scholar
  32. T. Watanabe, T. T. Wu, P. J. Catalano et al., “Molecular predictors of survival after adjuvant chemotherapy for colon cancer,” New England Journal of Medicine, vol. 344, no. 16, pp. 1196–1206, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. B. H. Kushner and N. K. V. Cheung, “Neuroblastoma—from genetic profiles to clinical challenge,” New England Journal of Medicine, vol. 353, no. 21, pp. 2215–2217, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. L. Mariani, G. Deiana, E. Vassella et al., “Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival in patients with diffuse WHO grade 2 gliomas treated without chemotherapy,” Journal of Clinical Oncology, vol. 24, no. 29, pp. 4758–4763, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Oudin, F. Bonnetain, R. Boidot et al., “Patterns of loss of heterozygosity in breast carcinoma during neoadjuvant chemotherapy,” International Journal of Oncology, vol. 30, no. 5, pp. 1145–1151, 2007. View at Google Scholar · View at Scopus
  36. C. H. Pui and W. E. Evans, “Treatment of acute lymphoblastic leukemia,” New England Journal of Medicine, vol. 354, no. 2, pp. 166–178, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. J. A. E. Irving, L. Bloodworth, N. P. Bown, M. C. Case, L. A. Hogarth, and A. G. Hall, “Loss of heterozygosity in childhood acute lymphoblastic leukemia detected by genome-wide microarray single nucleotide polymorphism analysis,” Cancer Research, vol. 65, no. 8, pp. 3053–3058, 2005. View at Google Scholar · View at Scopus
  38. C. G. Mullighan, S. Goorha, I. Radtke et al., “Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia,” Nature, vol. 446, no. 7137, pp. 758–764, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. C. G. Mullighan, C. B. Miller, I. Radtke et al., “BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros,” Nature, vol. 453, no. 7191, pp. 110–114, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. N. Kawamata, S. Ogawa, M. Zimmermann et al., “Molecular allelokaryotyping of pediatric acute lymphoblastic leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray,” Blood, vol. 111, no. 2, pp. 776–784, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. R. P. Kuiper, E. F. P. M. Schoenmakers, S. V. van Reijmersdal et al., “High-resolution genomic profiling of childhood ALL reveals novel recurrent genetic lesions affecting pathways involved in lymphocyte differentiation and cell cycle progression,” Leukemia, vol. 21, no. 6, pp. 1258–1266, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. J. D. Schiffman, Y. Wang, L. A. McPherson et al., “Molecular inversion probes reveal patterns of 9p21 deletion and copy number aberrations in childhood leukemia,” Cancer Genetics and Cytogenetics, vol. 193, no. 1, pp. 9–18, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. C. G. Mullighan, L. A. Phillips, X. Su et al., “Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia,” Science, vol. 322, no. 5906, pp. 1377–1380, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. J. J. Yang, D. Bhojwani, W. Yang et al., “Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia,” Blood, vol. 112, no. 10, pp. 4178–4183, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. J. D. Schiffman, J. G. Hodgson, S. R. VandenBerg et al., “Oncogenic BRAF mutation with CDKN2A inactivation is characteristic of a subset of pediatric malignant astrocytomas,” Cancer Research, vol. 70, no. 2, pp. 512–519, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. J. P. Robinson, M. W. Vanbrocklin, A. R. Guilbeault, D. L. Signorelli, S. Brandner, and S. L. Holmen, “Activated BRAF induces gliomas in mice when combined with Ink4a/Arf loss or Akt activation,” Oncogene, vol. 29, no. 3, pp. 335–344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. C. M. Hattinger, U. Pötschger, M. Tarkkanen et al., “Prognostic impact of chromosomal aberrations in Ewing tumours,” British Journal of Cancer, vol. 86, no. 11, pp. 1763–1769, 2002. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Ozaki, M. Paulussen, C. Poremba et al., “Genetic imbalances revealed by comparative genomic hybridization in Ewing tumors,” Genes Chromosomes and Cancer, vol. 32, no. 2, pp. 164–171, 2001. View at Google Scholar
  49. P. Roberts, S. A. Burchill, S. Brownhill et al., “Ploidy and karyotype complexity are powerful prognostic indicators in the Ewing's sarcoma family of tumors: a study by the United Kingdom cancer cytogenetics and the children's cancer and leukaemia group,” Genes Chromosomes and Cancer, vol. 47, no. 3, pp. 207–220, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. G. Neale, X. Su, C. L. Morton et al., “Molecular characterization of the pediatric preclinical testing panel,” Clinical Cancer Research, vol. 14, no. 14, pp. 4572–4583, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. G. Armengol, M. Tarkkanen, M. Virolainen et al., “Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization,” British Journal of Cancer, vol. 75, no. 10, pp. 1403–1409, 1997. View at Google Scholar · View at Scopus
  52. S. Brisset, G. Schleiermacher, M. Peter et al., “CGH analysis of secondary genetic changes in Ewing tumors: correlation with metastatic disease in a series of 43 cases,” Cancer Genetics and Cytogenetics, vol. 130, no. 1, pp. 57–61, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Savola, A. Klami, A. Tripathi et al., “Combined use of expression and CGH arrays pinpoints novel candidate genes in Ewing sarcoma family of tumors,” BMC Cancer, vol. 9, article 17, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Tarkkanen, S. Kiuru-Kuhlefelt, C. Blomqvist et al., “Clinical correlations of genetic changes by comparative genomic hybridization in Ewing sarcoma and related tumors,” Cancer Genetics and Cytogenetics, vol. 114, no. 1, pp. 35–41, 1999. View at Publisher · View at Google Scholar · View at Scopus
  55. D. C. Shing, C. A. Morley-Jacob, I. Roberts, E. Nacheva, and N. Coleman, “Ewing's tumour: novel recurrent chromosomal abnormalities demonstrated by molecular cytogenetic analysis of seven cell lines and one primary culture,” Cytogenetic and Genome Research, vol. 97, no. 1-2, pp. 20–27, 2002. View at Publisher · View at Google Scholar · View at Scopus
  56. B. I. Ferreira, J. Alonso, J. Carrillo et al., “Array CGH and gene-expression profiling reveals distinct genomic instability patterns associated with DNA repair and cell-cycle checkpoint pathways in Ewing's sarcoma,” Oncogene, vol. 27, no. 14, pp. 2084–2090, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. D. Maurici, A. Perez-Atayde, H. E. Grier, N. Baldini, M. Serra, and J. A. Fletcher, “Frequency and implications of chromosome 8 and 12 gains in Ewing sarcoma,” Cancer Genetics and Cytogenetics, vol. 100, no. 2, pp. 106–110, 1998. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Zielenska, Z. M. Zhang, K. Ng et al., “Acquisition of secondary structural chromosomal changes in pediatric Ewing sarcoma is a probable prognostic factor for tumor response and clinical outcome,” Cancer, vol. 91, no. 11, pp. 2156–2164, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. S. C. Brownhill, C. Taylor, and S. A. Burchill, “Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT,” British Journal of Cancer, vol. 96, no. 12, pp. 1914–1923, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Y. Huang, P. B. Illei, Z. Zhao et al., “Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse,” Journal of Clinical Oncology, vol. 23, no. 3, pp. 548–558, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. H. Kovar, G. Jug, D. N. T. Aryee et al., “Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors,” Oncogene, vol. 15, no. 18, pp. 2225–2232, 1997. View at Google Scholar · View at Scopus
  62. S. Savola, F. Nardi, K. Scotlandi, P. Picci, and S. Knuutila, “Microdeletions in 9p21.3 induce false negative results in CDKN2A FISH analysis of Ewing sarcoma,” Cytogenetic and Genome Research, vol. 119, no. 1-2, pp. 21–26, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. G. Wei, C. R. Antonescu, E. De Alava et al., “Prognostic impact of INK4A deletion in Ewing sarcoma,” Cancer, vol. 89, no. 4, pp. 793–799, 2000. View at Publisher · View at Google Scholar · View at Scopus
  64. J. A. López-Guerrero, A. Pellín, R. Noguera, C. Carda, and A. Llombart-Bosch, “Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors,” Laboratory Investigation, vol. 81, no. 6, pp. 803–814, 2001. View at Google Scholar · View at Scopus
  65. Y. Wang, V. E. Carlton, G. Karlin-Neumann et al., “High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays,” BMC Medical Genomics, vol. 2, article 8, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. F. Mugneret, S. Lizard, A. Aurias, and C. Turc-Carel, “Chromosomes in Ewing's sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16),” Cancer Genetics and Cytogenetics, vol. 32, no. 2, pp. 239–245, 1988. View at Google Scholar · View at Scopus
  67. S. Selvarajah, M. Yoshimoto, M. Prasad et al., “Characterization of trisomy 8 in pediatric undifferentiated sarcomas using advanced molecular cytogenetic techniques,” Cancer Genetics and Cytogenetics, vol. 174, no. 1, pp. 35–41, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. E. C. Douglass, S. T. Rowe, M. Valentine, D. Parham, W. H. Meyer, and E. I. Thompson, “A second nonrandom translocation, der(16)t(1;16)(q21;q13), in Ewing sarcoma and peripheral neuroectodermal tumor,” Cytogenetics and Cell Genetics, vol. 53, no. 2-3, pp. 87–90, 1990. View at Google Scholar · View at Scopus
  69. A. Forus, J. M. Berner, L. A. Meza-Zepeda et al., “Molecular characterization of a novel amplicon at 1q21-q22 frequently observed in human sarcomas,” British Journal of Cancer, vol. 78, no. 4, pp. 495–503, 1998. View at Google Scholar · View at Scopus
  70. D. Engelkamp, B. W. Schafer, M. G. Mattei, P. Erne, and C. W. Heizmann, “Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 14, pp. 6547–6551, 1993. View at Google Scholar · View at Scopus
  71. S. Knuutila, G. Armengol, A. M. Björkqvist et al., “Comparative genomic hybridization study on pooled DNAs from tumors of one clinical-pathological entity,” Cancer Genetics and Cytogenetics, vol. 100, no. 1, pp. 25–30, 1998. View at Publisher · View at Google Scholar · View at Scopus
  72. E. De Alava, C. R. Antonescu, A. Panizo et al., “Prognostic impact of P53 status in Ewing sarcoma,” Cancer, vol. 89, no. 4, pp. 783–792, 2000. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Shen, M. Platek, A. Mahasneh, C. B. Ambrosone, and H. Zhao, “Mitochondrial copy number and risk of breast cancer: a pilot study,” Mitochondrion, vol. 10, no. 1, pp. 62–68, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. J. Xing, M. Chen, C. G. Wood et al., “Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma,” Journal of the National Cancer Institute, vol. 100, no. 15, pp. 1104–1112, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Yu, Y. Wan, and Q. Zou, “Decreased copy number of mitochondrial DNA in ewing's sarcoma,” Clinica Chimica Acta, vol. 411, no. 9-10, pp. 679–683, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Yu, Y. Wan, Q. Zou, and Y. Xi, “High frequency of mitochondrial DNA D-loop mutations in Ewing's sarcoma,” Biochemical and Biophysical Research Communications, vol. 390, no. 3, pp. 447–450, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. P. A. Jones and S. B. Baylin, “The fundamental role of epigenetic events in cancer,” Nature Reviews Genetics, vol. 3, no. 6, pp. 415–428, 2002. View at Google Scholar · View at Scopus
  78. T. Tsuchiya, K. I. Sekine, S. I. Hinohara, T. Namiki, T. Nobori, and Y. Kaneko, “Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma,” Cancer Genetics and Cytogenetics, vol. 120, no. 2, pp. 91–98, 2000. View at Publisher · View at Google Scholar · View at Scopus
  79. K. Harada, S. Toyooka, A. Maitra et al., “Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines,” Oncogene, vol. 21, no. 27, pp. 4345–4349, 2002. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Avigad, S. Shukla, I. Naumov et al., “Aberrant methylation and reduced expression of RASSF1A in Ewing sarcoma,” Pediatric Blood and Cancer, vol. 53, no. 6, pp. 1023–1028, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Ebinger, L. Senf, O. Wachowski, and W. Scheurlen, “Promoter methylation pattern of caspase-8, P16INK4A, MGMT, TIMP-3, and E-cadherin in medulloblastoma,” Pathology and Oncology Research, vol. 10, no. 1, pp. 17–21, 2004. View at Google Scholar · View at Scopus
  82. S. Fulda, M. U. Küfer, E. Meyer, F. Van Valen, B. Dockhorn-Dworniczak, and K. M. Debatin, “Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer,” Oncogene, vol. 20, no. 41, pp. 5865–5877, 2001. View at Publisher · View at Google Scholar · View at Scopus
  83. A. Hurtubise, M. L. Bernstein, and R. L. Momparler, “Preclinical evaluation of the antineoplastic action of 5-aza-2′-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells,” Cancer Cell International, vol. 8, article 16, 2008. View at Publisher · View at Google Scholar · View at Scopus