Genetics and epigenetics of the TET-ETS translocation network

Genetics and Epigenetics

Volumn , Issue 2, 2009, Pages 1-15

  Staege, Martin S ^a   Max, Daniela ^a  

^a MARTIN LUTHER UNIVERSITÄT HALLE WITTENBERG   (Germany)

Author keywords

ETS transcription factors; Ewing family tumors; Gene fusions; Pseudogenes; TET family

Indexed keywords

EID: 75149166923     PISSN: None     EISSN: 1179237X     Source Type: Journal    
DOI: None     Document Type: Review

References (135)

1. Boerma EG, Siebert R, Kluin PM, Baudis M. Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge. Leukemia. 2009; 23:225-34.
2. Boxer LM, Dang CV. Translocations involving c-myc and c-myc function. Oncogene. 2001;20:5595-610.
3. Zimber-Strobl U, Strobl L, Höfelmayr H, et al. EBNA2 and c-myc in B cell immortalization by Epstein-Barr virus and in the pathogenesis of Burkitt's lymphoma. Curr Top Microbiol Immunol. 1999;246:315-20.
4. Pajic A, Staege MS, Dudziak D, et al. Antagonistic effects of c-myc and Epstein-Barr virus latent genes on the phenotype of human B cells. Int J Cancer. 2001;93:810-6.
5. Staege MS, Lee SP, Frisan T, et al. MYC overexpression imposes a nonimmunogenic phenotype on Epstein-Barr virus-infected B cells. Proc Natl Acad Sci U S A. 2002;99:4550-5.
6. Ewing J. Diffuse endothelioma of bone. Proc N Y Pathol Soc. 1921;21: 17-24.
7. Staege MS, Hutter C, Neumann I, et al. DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. Cancer Res. 2004;64:8213-21.
8. Riggi N, Suvà ML, Suvà D, et al. EWS-FLI-1 expression triggers a Ewing's sarcoma initiation program in primary human mesenchymal stem cells. Cancer Res. 2008;68:2176-85.
9. Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell. 2007;11: 421-9.
10. Richter GH, Plehm S, Fasan A, et al. EZH2 is a mediator of EWS/ FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation. Proc Natl Acad Sci U S A. 2009; 106:5324-9.
11. Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM. Chromosome study of Ewing's sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12). Cancer Genet Cytogenet. 1984;12:1-19.
12. May WA, Gishizky ML, Lessnick SL, et al. Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc Natl Acad Sci U S A. 1993;90:5752-6.
13. Zucman J, Delattre O, Desmaze C, et al. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet. 1993;4:341-5.
14. Hallor KH, Mertens F, Jin Y, et al. Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2005;44:97-102.
15. Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma-association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006;12:5356-62.
16. Antonescu CR, Dal Cin P, Nafa K, et al. EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2007;46:1051-60.
17. Panagopoulos I, Höglund M, Mertens F, Mandahl N, Mitelman F, Aman P. Fusion of the EWS and CHOP genes in myxoid liposarcoma. Oncogene. 1996;12:489-94.
18. Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT. A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet. 1994;6:146-51.
19. Jeon IS, Davis JN, Braun BS, et al. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995; 10:1229-34.
20. Kaneko Y, Yoshida K, Handa M, et al. Fusion of an ETS-family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer. 1996;15:115-21.
21. Peter M, Couturier J, Pacquement H, et al. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene. 1997;14:1159-64.
22. Szuhai K, Ijszenga M, de Jong D, Karseladze A, Tanke HJ, Hogendoorn PC. The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology. Clin Cancer Res. 2009;15:2259-68.
23. Labelle Y, Zucman J, Stenman G, et al. Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation. Hum Mol Genet. 1995;4:2219-26.
24. Mastrangelo T, Modena P, Tornielli S, et al. A novel zinc finger gene is fused to EWS in small round cell tumor. Oncogene. 2000;19:3799-804.
25. Brandal P, Panagopoulos I, Bjerkehagen B, et al. Detection of a t(1;22)(q23;q12) translocation leading to an EWSR1-PBX1 fusion gene in a myoepithelioma. Genes Chromosomes Cancer. 2008;47:558-64.
26. Yamaguchi S, Yamazaki Y, Ishikawa Y, Kawaguchi N, Mukai H, Nakamura T. EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22) (p21;q12). Genes Chromosomes Cancer. 2005;43:217-22.
27. Möller E, Stenman G, Mandahl N, et al. POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. J Pathol. 2008;215:78-86.
28. Wang L, Bhargava R, Zheng T, et al. Undifferentiated small round cell sarcomas with rare EWS gene fusions: identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV fusions. J Mol Diagn. 2007;9:498-509.
29. Gerald WL, Rosai J, Ladanyi M. Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor. Proc Natl Acad Sci U S A. 1995;92: 1028-32.
30. Martini A, La Starza R, Janssen H, et al. Recurrent rearrangement of the Ewing's sarcoma gene, EWSR1, or its homologue, TAF15, with the transcription factor CIZ/NMP4 in acute leukemia. Cancer Res. 2002;62:5408-12.
31. Mertens F, Fletcher CD, Antonescu CR, et al. Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Lab Invest. 2005;85: 408-15.
32. Storlazzi CT, Mertens F, Nascimento A, et al. Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma. Hum Mol Genet. 2003; 12:2349-58.
33. Guillou L, Benhattar J, Gengler C, et al. Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol. 2007;31:1387-402.
34. Rabbitts TH, Forster A, Larson R, Nathan P. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet. 1993;4:175-80.
35. Shing DC, McMullan DJ, Roberts P, et al. FUS/ERG gene fusions in Ewing's tumors. Cancer Res. 2003;63:4568-76.
36. Panagopoulos I, Aman P, Fioretos T, et al. Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Genes Chromosomes Cancer. 1994;11:256-62.
37. Ichikawa H, Shimizu K, Hayashi Y, Ohki M. An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res. 1994;54:2865-8.
38. Kong XT, Ida K, Ichikawa H, et al. Consistent detection of TLS/ FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript. Blood. 1997; 90:1192-9.
39. Pallisgaard N, Hokland P, Riishøj DC, Pedersen B, Jørgensen P. Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia. Blood. 1998;92:574-88.
40. Ng TL, O'Sullivan MJ, Pallen CJ, et al. Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn. 2007;9:459-63.
41. Attwooll C, Tariq M, Harris M, Coyne JD, Telford N, Varley JM. Identification of a novel fusion gene involving hTAFII68 and CHN from a t(9;17)(q22;q11.2) translocation in an extraskeletal myxoid chondrosarcoma. Oncogene. 1999;18:7599-601.
42. Laudet V, Hänni C, Stéhelin D, Duterque-Coquillaud M. Molecular phylogeny of the ETS gene family. Oncogene. 1999;18:1351-9.
43. Kawamura-Saito M, Yamazaki Y, Kaneko K, et al. Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation. Hum Mol Genet. 2006;15:2125-37.
44. Tomlins SA, Laxman B, Dhanasekaran SM, et al. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature. 2007;448:595-9.
45. Hermans KG, Bressers AA, van der Korput HA, Dits NF, Jenster G, Trapman J. Two unique novel prostate-specific and androgen-regulated fusion partners of ETV4 in prostate cancer. Cancer Res. 2008;68: 3094-8.
46. Han B, Mehra R, Dhanasekaran SM, et al. A fluorescence in situ hybridization screen for E26 transformation-specific aberrations: identification of DDX5-ETV4 fusion protein in prostate cancer. Cancer Res. 2008;68:7629-37.
47. Tomlins SA, Rhodes DR, Perner S, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310: 644-8.
48. Tomlins SA, Mehra R, Rhodes DR, et al. TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res. 2006; 66:3396-400.
49. Helgeson BE, Tomlins SA, Shah N, et al. Characterization of TMPRSS2: ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer. Cancer Res. 2008;68:73-80.
50. Attard G, Clark J, Ambroisine L, et al. Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer. Br J Cancer. 2008; 99:314-20.
51. Hermans KG, van der Korput HA, van Marion R, et al. Truncated ETV1, fused to novel tissue-specific genes, and full-length ETV1 in prostate cancer. Cancer Res. 2008;68:7541-9.
52. Maher CA, Kumar-Sinha C, Cao X, et al. Transcripome sequencing to detect gene fusion in cancer. Nature. 2009;458:97-101.
53. Moore SD, Offor O, Ferry JA, Amrein PC, Morton CC, Dal Cin P. ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X;21) (q25-26;q22). Leuk Res. 2006;30:1037-42.
54. Biedler JL, Helson L, Spengler BA. Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res. 1973;33:2643-52.
55. Mizushima S, Nagata S. pEF-BOS, a powerful mammalian expression vector. Nucleic Acids Res. 1990;18:5322.
56. Kanda T, Sullivan KF, Wahl GM. Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr Biol. 1998;8:377-85.
57. Mitelman F, Johansson B, Mertens F. Mitelman Database of Chromosome Aberrations in Cancer. Available at: http://cgap.nci.nih.gov/Chromosomes/Mitelman Accessed June 17 2009.
58. Altschul SF, Madden TL, Schäffer AA, et al. Gapped BLAST and PSIBLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997;25:3389-402.
59. Giard DJ, Aaronson SA, Todaro GJ, et al. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973;51:1417-23.
60. Nicholas, KB, Nicholas HB Jr. GeneDoc: a tool for editing and annotating multiple sequence alignments. 1997. Available at: http://www.nrbsc.org/ Accessed June 17 2009.
61. Nourse J, Mellentin JD, Galili N, et al. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell. 1990;60:535-45.
62. Zhong CH, Prima V, Liang X, et al. E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3;p13.3) in acute leukemia. Leukemia. 2008;22:723-9.
63. Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K. Structure, mapping and expression of a human NOR-1 gene, the third member of the Nur77/NGFI-B family. Biochim Biophys Acta. 1996;1308: 205-14.
64. Sjögren H, Wedell B, Meis-Kindblom JM, Kindblom LG, Stenman G. Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21). Cancer Res. 2000;60:6832-5.
65. Hisaoka M, Ishida T, Imamura T, Hashimoto H. TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer. 2004;40:325-8.
66. Mencinger M, Panagopoulos I, Andreasson P, Lassen C, Mitelman F, Aman P. Characterization and chromosomal mapping of the human TFG gene involved in thyroid carcinoma. Genomics. 1997;41:327-31.
67. Yagasaki F, Jinnai I, Yoshida S, et al. Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13). Genes Chromosomes Cancer. 1999;26:192-202.
68. Mao X, Miesfeldt S, Yang H, Leiden JM, Thompson CB. The FLI-1 and chimeric EWS-FLI-1 oncoproteins display similar DNA binding specificities. J Biol Chem. 1994;269:18216-22.
69. May WA, Lessnick SL, Braun BS, et al. The Ewing's sarcoma EWS/ FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. Mol Cell Biol. 1993;13: 7393-8.
70. Guillon N, Tirode F, Boeva V, Zynovyev A, Barillot E, Delattre O. The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function. PLoS One. 2009;4: e4932.
71. Ohno T, Rao VN, Reddy ES. EWS/FLI-1 chimeric protein is a transcriptional activator. Cancer Res. 1993;53:5859-63.
72. Welford SM, Hebert SP, Deneen B, Arvand A, Denny CT. DNA binding domain-independent pathways are involved in EWS/FLI1-mediated oncogenesis. J Biol Chem. 2001;276:41977-84.
73. Yang L, Chansky HA, Hickstein DD. EWS/FLI-1 fusion protein interacts with hyperphosphorylated RNA polymerase II and interferes with serine-arginine protein-mediated RNA splicing. J Biol Chem. 2000;275: 37612-8.
74. Knoop LL, Baker SJ. EWS/FLI alters 5'-splice site selection. J Biol Chem. 2001;276:22317-22.
75. Chansky HA, Hu M, Hickstein DD, Yang L. Oncogenic TLS/ERG and EWS/Fli-1 fusion proteins inhibit RNA splicing mediated by YB-1 protein. Cancer Res. 2001;61:3586-90.
76. Ohkura N, Yaguchi H, Tsukada T, Yamaguchi K. The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing. J Biol Chem. 2002;277:535-43.
77. Lerga A, Hallier M, Delva L, et al. Identification of an RNA binding specificity for the potential splicing factor TLS. J Biol Chem. 2001;276: 6807-16.
78. Yang L, Embree LJ, Tsai S, Hickstein DD. Oncoprotein TLS interacts with serine-arginine proteins involved in RNA splicing. J Biol Chem. 1998; 273:27761-4.
79. Meissner M, Lopato S, Gotzmann J, Sauermann G, Barta A. Protooncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins. Exp Cell Res. 2003; 283:184-95.
80. Embree LJ, Azuma M, Hickstein DD. Ewing sarcoma fusion protein EWSR1/FLI1 interacts with EWSR1 leading to mitotic defects in zebrafish embryos and human cell lines. Cancer Res. 2009;69:4363-71.
81. Armengol G, Tarkkanen M, Virolainen M, et al. Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization. Br J Cancer. 1997;75:1403-9.
82. Roberts P, Burchill SA, Brownhill S, 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 Cancer. 2007;47:207-20.
83. Khan J, Klein JS, Ringner M, et al. Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. Nat Med. 2001;7:673-9.
84. Staege MS, Hattenhorst UE, Neumann UE, Hutter C, Foja S, Burdach S. DNA-microarrays as tools for the identification of tumor specific gene expression profiles: applications in tumor biology, diagnosis and therapy. Klin Padiatr. 2003;215:135-9.
85. Thompson AD, Braun BS, Arvand A, et al. EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's sarcoma EWS/FLI1 fusion gene. Oncogene. 1996;13:2649-58.
86. May WA, Arvand A, Thompson AD, Braun BS, Wright M, Denny CT. EWS/FLI1-induced manic fringe renders NIH 3T3 cells tumorigenic. Nat Genet. 1997;17:495-7.
87. Zwerner JP, May WA. PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors. Oncogene. 2001;20:626-33.
88. Matsumoto Y, Tanaka K, Nakatani F, Matsunobu T, Matsuda S, Iwamoto Y. Downregulation and forced expression of EWS-FLI1 fusion gene results in changes in the expression of G(1)regulatory genes. Br J Cancer. 2001; 84:768-75.
89. Dauphinot L, De Oliveira C, Melot T, et al. Analysis of the expression of cell cycle regulators in Ewing cell lines: EWS-FLI-1 modulates p57KIP2 and c-Myc expression. Oncogene. 2001;20:3258-65.
90. Takahashi A, Higashino F, Aoyagi M, et al. EWS/ETS fusions activate telomerase in Ewing's tumors. Cancer Res. 2003;63:8338-44.
91. Deneen B, Welford SM, Ho T, Hernandez F, Kurland I, Denny CT. PIM3 proto-oncogene kinase is a common transcriptional target of divergent EWS/ETS oncoproteins. Mol Cell Biol. 2003;23:3897-908.
92. García-Aragoncillo E, Carrillo J, Lalli E, et al. DAX1, a direct target of EWS/FLI1 oncoprotein, is a principal regulator of cell-cycle progression in Ewing's tumor cells. Oncogene. 2008;27:6034-43.
93. Nishimori H, Sasaki Y, Yoshida K, et al. The Id2 gene is a novel target of transcriptional activation by EWS-ETS fusion proteins in Ewing family tumors. Oncogene. 2002;21:8302-9.
94. Smith R, Owen LA, Trem DJ, et al. Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma. Cancer Cell. 2006;9:405-16.
95. Miyagawa Y, Okita H, Itagaki M, et al. EWS/ETS regulates the expression of the Dickkopf family in Ewing family tumor cells. PLoS ONE. 2009; 4:e4634.
96. Kinsey M, Smith R, Lessnick SL. NR0B1 is required for the oncogenic phenotype mediated by EWS/FLI in Ewing's sarcoma. Mol Cancer Res. 2006;4:851-9.
97. Im YH, Kim HT, Lee C, et al. EWS-FLI1, EWS-ERG, and EWSETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor beta type II receptor gene. Cancer Res. 2000;60:1536-40.
98. Potikyan G, Savene RO, Gaulden JM, et al. EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins. Cancer Res. 2007;67:6675-84.
99. Kauer M, Ban J, Kofler R, et al. A molecular function map of Ewing's sarcoma. PLoS One. 2009;4:e5415.
100. Thompson AD, Teitell MA, Arvand A, Denny CT. Divergent Ewing's sarcoma EWS/ETS fusions confer a common tumorigenic phenotype on NIH3T3 cells. Oncogene. 1999;18:5506-13.
101. Braunreiter CL, Hancock JD, Coffin CM, Boucher KM, Lessnick SL. Expression of EWS-ETS fusions in NIH3T3 cells reveals significant differences to Ewing's sarcoma. Cell Cycle. 2006;5:2753-9.
102. Zou J, Ichikawa H, Blackburn ML, et al. The oncogenic TLS-ERG fusion protein exerts different effects in hematopoietic cells and fibroblasts. Mol Cell Biol. 2005;25:6235-46.
103. Bandrés E, Malumbres R, Escalada A, et al. Gene expression profile of ewing sarcoma cell lines differing in their EWS-FLI1 fusion type. J Pediatr Hematol Oncol. 2005;27:537-42.
104. Aryee DN, Sommergruber W, Muehlbacher K, Dockhorn-Dworniczak B, Zoubek A, Kovar H. Variability in gene expression patterns of Ewing tumor cell lines differing in EWS-FLI1 fusion type. Lab Invest. 2000;80: 1833-44.
105. de Alava E, Kawai A, Healey JH, et al. EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol. 16:1248-55.
106. Ohali A, Avigad S, Zaizov R, et al. Prediction of high risk Ewing's sarcoma by gene expression profiling. Oncogene. 2004;23:8997-9006.
107. Schaefer KL, Eisenacher M, Braun Y, et al. Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy. Eur J Cancer. 2008;44:699-709.
108. Scotlandi K, Remondini D, Castellani G, et al. Overcoming resistance to conventional drugs in Ewing sarcoma and identification of molecular predictors of outcome. J Clin Oncol. 2009;27:2209-16.
109. Savola S, Klami A, Tripathi A, et al. Combined use of expression and CGH arrays pinpoints novel candidate genes in Ewing sarcoma family of tumors. BMC Cancer. 2009;9:17.
110. Bielack SS, Paulussen M, Köhler G. A patient with two Ewing's sarcomas with distinct EWS fusion transcripts. N Engl J Med. 2004; 350:1364-5.
111. Hu-Lieskovan S, Heidel JD, Bartlett DW, Davis ME, Triche TJ. Sequencespecific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. Cancer Res. 2005;65:8984-92.
112. Maksimenko A, Lambert G, Bertrand JR, Fattal E, Couvreur P, Malvy C. Therapeutic potentialities of EWS-FLI-1 mRNA-targeted vectorized antisense oligonucleotides. Ann N Y Acad Sci. 2003;1002:72-7.
113. Toub N, Bertrand JR, Tamaddon A, et al. Efficacy of siRNA nanocapsules targeted against the EWS-FLI1 oncogene in Ewing sarcoma. Pharm Res. 2006;23:892-900.
114. Hühn R, Staege MS, Hesse M, Liebig L, Burdach SEG. Ceavage of the Ewing tumour-specific EWSR1-FLI1 mRNA by hammerhead ribozymes. Anticancer Res. 2009;29:1901-8.
115. Teitell MA, Thompson AD, Sorensen PH, Shimada H, Triche TJ, Denny CT. EWS/ETS fusion genes induce epithelial and neuroectodermal differentiation in NIH 3T3 fibroblasts. Lab Invest. 1999; 79:1535-43.
116. Hu-Lieskovan S, Zhang J, Wu L, Shimada H, Schofield DE, Triche TJ. EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing's family of tumors. Cancer Res. 2005;65:4633-44.
117. Yang Y, Zhang L, Wei Y, et al. Neural differentiation arrest in embryonal carcinoma cells with forced expression of EWS-FLI1. J Neurooncol. 2008;90:141-50.
118. Coles EG, Lawlor ER, Bronner-Fraser M. EWS-FLI1 causes neuroepithelial defects and abrogates emigration of neural crest stem cells. Stem Cells. 2008;26:2237-44.
119. Young PJ, Francis JW, Lince D, Coon K, Androphy EJ, Lorson CL. The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor neuron protein. Brain Res Mol Brain Res. 2003;119:37-49.
120. Vance C, Rogelj B, Hortobágyi T, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009;323:1208-11.
121. Li H, Watford W, Li C, Parmelee A, et al. Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development. J Clin Invest. 2007;117:1314-23.
122. Torchia EC, Boyd K, Rehg JE, Qu C, Baker SJ. EWS/FLI-1 induces rapid onset of myeloid/erythroid leukemia in mice. Mol Cell Biol. 2007;27: 7918-34.
123. Lin PP, Pandey MK, Jin F, et al. EWS-FLI1 induces developmental abnormalities and accelerates sarcoma formation in a transgenic mouse model. Cancer Res. 2008;68:8968-75.
124. Foell JL, Hesse M, Volkmer I, Schmiedel BJ, Neumann I, Staege MS. Membrane-associated phospholipase A1 beta (LIPI) Is an Ewing tumourassociated cancer/testis antigen. Pediatr Blood Cancer. 2008;51: 228-34.
125. Suvà ML, Riggi N, Stehle JC, et al. Identification of cancer stem cells in Ewing's sarcoma. Cancer Res. 2009;69:1776-81.
126. Mueller T, Luetzkendorf J, Nerger K, Schmoll HJ, Mueller LP. Analysis of OCT4 expression in an extended panel of human tumor cell lines from multiple entities and in human mesenchymal stem cells. Cell Mol Life Sci. 2009;66:495-503.
127. Kucia M, Wysoczynski M, Ratajczak J, Ratajczak MZ. Identification of very small embryonic like (VSEL) stem cells in bone marrow. Cell Tissue Res. 2008;331:125-34.
128. Sauerzweig S, Munsch T, Lessmann V, Reymann KG, Braun H. A population of serum deprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells. Exp Cell Res. 2009;315:50-66.
129. López-Guerrero JA, Pellín A, Noguera R, Carda C, Llombart-Bosch A. Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors. Lab Invest. 2001;81:803-14.
130. Sakimura R, Tanaka K, Nakatani F, et al. Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors. Int J Cancer. 2005;116:784-92.
131. Hurtubise A, Bernstein ML, Momparler RL. Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells. Cancer Cell Int. 2008;8:16.
132. Iljin K, Wolf M, Edgren H, et al. TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. Cancer Res. 2006;66:10242-6.
133. Burdach S, Plehm S, Unland R, et al. Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2. Cell Cycle. 2009;8:1991-6.
134. Perani M, Antonson P, Hamoudi R, et al.The proto-oncoprotein SYT interacts with SYT-interacting protein/co-activator activator (SIP/CoAA), a human nuclear receptor co-activator with similarity to EWS and TLS/ FUS family of proteins. J Biol Chem. 2005;280:42863-76.
135. Bovée JV, Devilee P, Cornelisse CJ, Schuuring E, Hogendoorn PC. Identification of an EWS-pseudogene using translocation detection by RT-PCR in Ewing's sarcoma. Biochem Biophys Res Commun. 1995;213:1051-60.