Molecular detection and targeting of EWSR1 fusion transcripts in soft tissue tumors

Medical Oncology

Volumn 30, Issue 1, 2013, Pages

  Cantile, Monica ^a   Marra, Laura ^a   Franco, Renato ^a   Ascierto, Paolo ^a   Liguori, Giuseppina ^a   De Chiara, Annarosaria ^a   Botti, Gerardo ^a  

^a NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

EWSR1 partners; Fusion transcript detection; Fusion transcript inhibition

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 1; ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; CHIMERIC PROTEIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; FIGITUMUMAB; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; NANOCAPSULE; NUCLEAR FACTOR OF ACTIVATED T CELLS CYTOPLASMIC CALCINEURIN DEPENDENT 2; NUCLEAR RECEPTOR NR4A3; OCTAMER TRANSCRIPTION FACTOR 4; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE; RNA BINDING PROTEIN EWS; SMALL INTERFERING RNA; TIVANTINIB; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR DUX4; TRANSCRIPTION FACTOR ER81; TRANSCRIPTION FACTOR ERG; TRANSCRIPTION FACTOR ETS; TRANSCRIPTION FACTOR ETV4; TRANSCRIPTION FACTOR FEV; TRANSCRIPTION FACTOR FLI 1; TRANSCRIPTION FACTOR PBX1; TRANSCRIPTION FACTOR SMARCA5; TRANSCRIPTION FACTOR SP3; TRANSCRIPTION FACTOR ZNF278; TRANSCRIPTION FACTOR ZNF384; UBIQUINOL CYTOCHROME C REDUCTASE HINGE PROTEIN; UNCLASSIFIED DRUG; YK 4279; CALMODULIN BINDING PROTEIN; EWSR1 PROTEIN, HUMAN; ONCOPROTEIN; RNA BINDING PROTEIN;

AMINO TERMINAL SEQUENCE; ANGIOGENESIS; APOPTOSIS; CANCER CLASSIFICATION; CARCINOGENESIS; CELL DEDIFFERENTIATION; CELL FUNCTION; CELL PROLIFERATION; CHONDROSARCOMA; CHROMOSOME ABERRATION; CHROMOSOME BREAKAGE; CHROMOSOME REARRANGEMENT; CHROMOSOME TRANSLOCATION; DESMOPLASTIC SMALL ROUND CELL TUMOR; DOWN REGULATION; DRUG MECHANISM; DRUG TARGETING; EWING SARCOMA; EWING SARCOMA BREAKPOINT REGION 1 GENE; EXON; EXTRASKELETAL MYXOID CHONDROSARCOMA; FLUORESCENCE IN SITU HYBRIDIZATION; FUSION GENE; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE LOCUS; GENE PROBE; GENE SEQUENCE; GENE STRUCTURE; HISTIOCYTOMA; HISTOGENESIS; HUMAN; KARYOTYPE; LABORATORY DEVICE; LIVER CELL CARCINOMA; MOLECULAR BIOLOGY; MOLECULAR GENETICS; MORPHOLOGY; MYOEPITHELIOMA; NEUROECTODERM TUMOR; NONHUMAN; ONCOGENE; OSTEOSARCOMA; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; QUALITATIVE ANALYSIS; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; RHABDOMYOSARCOMA; SARCOMATOUS HEPATOCELLULAR CARCINOMA; SMALL CELL OSTEOSARCOMA; SMALL CELL SARCOMA; SOFT TISSUE SARCOMA; SOFT TISSUE TUMOR; UPREGULATION; WESTERN BLOTTING; GENETICS;

CALMODULIN-BINDING PROTEINS; HUMANS; ONCOGENE PROTEINS, FUSION; RNA-BINDING PROTEINS; SOFT TISSUE NEOPLASMS;

MLCS; MLOWN;

EID: 84880591056     PISSN: 13570560     EISSN: 1559131X     Source Type: Journal    
DOI: 10.1007/s12032-012-0412-8     Document Type: Review

References (120)

1. Plougastel B, Mattei MG, Thomas G, Delattre O. Cloning and chromosome localization of the mouse Ews gene. Genomics. 1994;23:278-81.
2. Plougastel B, Zucman J, Peter M, Thomas G, Delattre O. Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation. Genomics. 1993;18:609-15.
3. Sankar S, Lessnick SL. Promiscuous partnerships in Ewing's sarcoma. Cancer Genet. 2011;204:351-65.
4. Azuma M, Embree LJ, Sabaawy H, Hickstein DD. Ewing sarcoma protein EWSR1 maintains mitotic integrity and proneural cell survival in the zebrafish embryo. PLoS ONE. 2007;2:e979.
5. Rossow KL, Janknecht R. The Ewing's sarcoma gene product functions as a transcriptional activator. Cancer Res. 2001;61:2690-5.
6. Araya N, Hirota K, Shimamoto Y, Miyagishi M, Yoshida E, Ishida J, Kaneko S, Kaneko M, Nakajima T, Fukamizu A. Cooperative interaction of EWS with CREB-binding protein selectively activates hepatocyte nuclear factor 4-mediated transcription. J Biol Chem. 2003;278:5427-32.
7. Gascoyne DM, Thomas GR, Latchman DS. The effects of Brn-3a on neuronal differentiation and apoptosis are differentially modulated by EWS and its oncogenic derivative EWS/Fli-1. Oncogene. 2004;23:3830-40.
8. Lee J, Rhee BK, Bae GY, Han YM, Kim J. Stimulation of Oct-4 activity by Ewing's sarcoma protein. Stem Cells. 2005;23:738-51.
9. Tannukit S, Wen X, Wang H, Paine ML. TFIP11, CCNL1 and EWSR1 protein-protein interactions, and their nuclear localization. Int J Mol Sci. 2008;9:1504-14.
10. Alliegro MC, Alliegro MA. A nuclear protein regulated during the transition from active to quiescent phenotype in cultured endothelial cells. Dev Biol. 1996;174:288-97.
11. Andersson MK, Ståhlberg A, Arvidsson Y, Olofsson A, Semb H, Stenman G, Nilsson O, Aman P. The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol. 2008;9:37.
12. Belyanskaya LL, Delattre O, Gehring H. Expression and subcellular localization of Ewing sarcoma (EWS) protein is affected by the methylation process. Exp Cell Res. 2003;288:374-81.
13. Leemann-Zakaryan RP, Pahlich S, Sedda MJ, Quero L, Grossenbacher D, Gehring H. Dynamic subcellular localization of the Ewing sarcoma proto-oncoprotein and its association with and stabilization of microtubules. J Mol Biol. 2009;386:1-13.
14. Bergeron D, Poliquin L, Kozak CA, Rassart E. Identification of a common viral integration region in Cas-Br-E murine leukemia virus-induced non-T-, non-B-cell lymphomas. J Virol. 1991;65:7-15.
15. Schoch C, Rieder H, Freund M, Hoelzer D, Riehm H, Fonatsch C. Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23): the implication of additional chromosomal aberrations. Ann Hematol. 1995;70:195-201.
16. Bailly RA, Bosselut R, Zucman J, Cormier F, Delattre O, Roussel M, Thomas G, Ghysdael J. DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol Cell Biol. 1994;14:3230-41.
17. Dauphinot L, De Oliveira C, Melot T, Sevenet N, Thomas V, Weissman BE, Delattre O. 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.
18. Li Y, Tanaka K, Fan X, Nakatani F, Li X, Nakamura T, Takasaki M, Yamamoto S, Iwamoto Y. Inhibition of the transcriptional function of p53 by EWS-Fli1 chimeric protein in Ewing family tumors. Cancer Lett. 2010;294:57-65.
19. Joo J, Christensen L, Warner K, States L, Kang HG, Vo K, Lawlor ER, May WA. GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors. PLoS ONE. 2009;4:e7608.
20. Li X, McGee-Lawrence ME, Decker M, Westendorf JJ. The Ewing's sarcoma fusion protein, EWS-FLI, binds Runx2 and blocks osteoblast differentiation. J Cell Biochem. 2010;111:933-43.
21. Riggi N, Suvà ML, De Vito C, Provero P, Stehle JC, Baumer K, Cironi L, Janiszewska M, Petricevic T, Suvà D, Tercier S, Joseph JM, Guillou L, Stamenkovic I. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells. Genes Dev. 2010;24:916-32.
22. De Vito C, Riggi N, Suvà ML, Janiszewska M, Horlbeck J, Baumer K, Provero P, Stamenkovic I. Let-7a is a direct EWS-FLI-1 target implicated in Ewing's sarcoma development. PLoS ONE. 2011;6:e23592.
23. Quezado M, Benjamin DR, Tsokos M. EWS/FLI-1 fusion transcripts in three peripheral primitive neuroectodermal tumors of the kidney. Hum Pathol. 1997;28:767-71.
24. Downing JR, Khandekar A, Shurtleff SA, Head DR, Parham DM, Webber BL, Pappo AS, Hulshof MG, Conn WP, Shapiro DN. Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma. Am J Pathol. 1995;146:626-34.
25. Burchill SA, Wheeldon J, Cullinane C, Lewis IJ. EWS-FLI1 fusion transcripts identified in patients with typical neuroblastoma. Eur J Cancer. 1997;33:239-43.
26. Scotlandi K, Chano T, Benini S, Serra M, Manara MC, Cerisano V, Picci P, Baldini N. Identification of EWS/FLI-1 transcripts in giant-cell tumor of bone. Int J Cancer. 2000;87:328-35.
27. Loughran SJ, Kruse EA, Hacking DF, de Graaf CA, Hyland CD, Willson TA, Henley KJ, Ellis S, Voss AK, Metcalf D, Hilton DJ, Alexander WS, Kile BT. The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol. 2008;9:810-9.
28. Zoubek A, Pfleiderer C, Salzer-Kuntschik M, Amann G, Windhager R, Fink FM, Koscielniak E, Delattre O, Strehl S, Ambros PF, et al. Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. Br J Cancer. 1994;70:908-13.
29. Im YH, Kim HT, Lee C, Poulin D, Welford S, Sorensen PH, Denny CT, Kim SJ. EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor beta type II receptor gene. Cancer Res. 2000;60:1536-40.
30. Matsui Y, Chansky HA, Barahmand-Pour F, Zielinska-Kwiatkowska A, Tsumaki N, Myoui A, Yoshikawa H, Yang L, Eyre DR. COL11A2 collagen gene transcription is differentially regulated by EWS/ERG sarcoma fusion protein and wild-type ERG. J Biol Chem. 2003;278:11369-75.
31. Irifune H, Nishimori H, Watanabe G, Yoshida K, Ikeda T, Matsui C, Morohashi M, Kawaguchi S, Nagoya S, Wada T, Yamashita T, Nakamura Y, Tokino T. Aberrant laminin beta3 isoforms downstream of EWS-ETS fusion genes in Ewing family tumors. Cancer Biol Ther. 2005;4:449-55.
32. Minoletti F, Sozzi G, Tornielli S, Pilotti S, Azzarelli A, Pierotti MA, Radice P. A novel EWS-ERG rearrangement generating two hybrid mRNAs in a peripheral primitive neuroectodermal tumour (pPNET) with a t(15;22) translocation. J Pathol. 1998;186:434-7.
33. Ordi J, de Alava E, Torné A, Mellado B, Pardo-Mindan J, Iglesias X, Cardesa A. Intraabdominal desmoplastic small round cell tumor with EWS/ERG fusion transcript. Am J Surg Pathol. 1998;22:1026-32.
34. Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H, Delattre O. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene. 1997;14:1159-64.
35. Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene. 1995;10:1229-34.
36. Ishida S, Yoshida K, Kaneko Y, Tanaka Y, Sasaki Y, Urano F, Umezawa A, Hata J, Fujinaga K. The genomic breakpoint and chimeric transcripts in the EWSR1-ETV4/E1AF gene fusion in Ewing sarcoma. Cytogenet Cell Genet. 1998;82:278-83.
37. Teitell MA, Thompson AD, Sorensen PH, Shimada H, Triche TJ, Denny CT. EWS/ETS fusion genes induce epithelial and neuroectodermal differentiation in NIH3T3 fibroblasts. Lab Invest. 1999;79:1535-43.
38. Llombart-Bosch A, Pellín A, Carda C, Noguera R, Navarro S, Peydró-Olaya A. Soft tissue Ewing sarcoma-peripheral primitive neuroectodermal tumor with atypical clear cell pattern shows a new type of EWS-FEV fusion transcript. Diagn Mol Pathol. 2000;9:137-44.
39. 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.
40. Antonescu CR, Zhang L, Chang NE, Pawel BR, Travis W, Katabi N, Edelman M, Rosenberg AE, Nielsen GP. Dal Cin P, Fletcher CD. EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosomes Cancer. 2010;49:1114-24.
41. Fujino T, Nomura K, Ishikawa Y, Makino H, Umezawa A, Aburatani H, Nagasaki K, Nakamura T. Function of EWS-POU5F1 in sarcomagenesis and tumor cell maintenance. Am J Pathol. 2010;176:1973-82.
42. Brandal P, Panagopoulos I, Bjerkehagen B, Gorunova L, Skjeldal S, Micci F, Heim S. 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.
43. Sirvent N, Trassard M, Ebran N, Attias R, Pedeutour F. Fusion of EWSR1 with the DUX4 facioscapulohumeral muscular dystrophy region resulting from t(4;22)(q35;q12) in a case of embryonal rhabdomyosarcoma. Cancer Genet Cytogenet. 2009;195:12-8.
44. Italiano A, Sung YS, Zhang L, Singer S, Maki RG, Coindre JM, Antonescu CR. High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas. Genes Chromosomes Cancer. 2012;51:207-18.
45. Laity JH, Lee BM, Wright PE. Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol. 2001;11:39-46.
46. Ladomery M, Dellaire G. Multifunctional zinc finger proteins in development and disease. Ann Hum Genet. 2002;66:331-42.
47. Mastrangelo T, Modena P, Tornielli S, Bullrich F, Testi MA, Mezzelani A, Radice P, Azzarelli A, Pilotti S, Croce CM, Pierotti MA, Sozzi G. A novel zinc finger gene is fused to EWS in small round cell tumor. Oncogene. 2000;19:3799-804.
48. 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 USA. 1995;92:1028-32.
49. Shimizu Y, Mitsui T, Kawakami T, Ikegami T, Kanazawa C, Katsuura M, Obata K, Yamagiwa I, Hayasaka K. Novel breakpoints of the EWS gene and the WT1 gene in a desmoplastic small round cell tumor. Cancer Genet Cytogenet. 1998;106:156-8.
50. Lee SB, Kolquist KA, Nichols K, Englert C, Maheswaran S, Ladanyi M, Gerald WL, Haber DA. The EWS-WT1 translocation product induces PDGFA in desmoplastic small round-cell tumour. Nat Genet. 1997;17:309-13.
51. Werner H, Idelman G, Rubinstein M, Pattee P, Nagalla SR, Roberts CT Jr. A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene. Cancer Lett. 2007;247:84-90.
52. Tian X, Sun D, Zhang Y, Zhao S, Xiong H, Fang J. Zinc finger protein 278, a potential oncogene in human colorectal cancer. Acta Biochim Biophys Sin (Shanghai). 2008;40:289-96.
53. Fedele M, Franco R, Salvatore G, Paronetto MP, Barbagallo F, Pero R, Chiariotti L, Sette C, Tramontano D, Chieffi G, Fusco A, Chieffi P. PATZ1 gene has a critical role in the spermatogenesis and testicular tumours. J Pathol. 2008;215:39-47.
54. Martini A, La Starza R, Janssen H, Bilhou-Nabera C, Corveleyn A, Somers R, Aventin A, Foà R, Hagemeijer A, Mecucci C, Marynen P. 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.
55. Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS. Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in extrascheletric myxoid chondrosarcoma. Oncogene. 1996;12:229-35.
56. Brody RI, Ueda T, Hamelin A, Jhanwar SC, Bridge JA, Healey JH, Huvos AG, Gerald WL, Ladanyi M. Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. Am J Pathol. 1997;150:1049-58.
57. Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, Fletchers CDM, Aurias A, Thomas G. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet. 1993;4:341-5.
58. Hiraga H, Nojima T, Abe S, Yamashiro K, Yamawaki S, Kaneda K, Nagashima K. Establishment of a new continuous clear cell sarcoma cell line. Morphological and cytogenetic characterization and detection of chimaeric EWS/ATF-1 transcripts. Virchows Arch. 1997;431:45-51.
59. Hallor KH, Mertens F, Jin Y, Meis-Kindblom JM, Kindblom LG, Behrendtz M, Kalén A, Mandahl N, Panagopoulos I. 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.
60. Hallor KH, Micci F, Meis-Kindblom JM, Kindblom LG, Bacchini P, Mandahl N, Mertens F, Panagopoulos I. Fusion genes in angiomatoid fibrous histiocytoma. Cancer Lett. 2007;251:158-63.
61. Rossi S, Szuhai K, Ijszenga M, Tanke HJ, Zanatta L, Sciot R, Fletcher CD. Dei Tos AP, Hogendoorn PC. EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. Clin Cancer Res. 2007;13:7322-8.
62. Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, Perez-Ordoñez B, Have C, Asa SL, Leong IT, Bradley G, Klieb H. Weinreb I EWSR1-ATF1 fusion is a novel and consistent finding in Hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer. 2011;50:559-70.
63. Flucke U, Mentzel T, Verdijk MA, Slootweg PJ, Creytens DH, Suurmeijer AJ, Tops BB. EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report. Hum Pathol. 2012;43:764-8.
64. Thway K, Nicholson AG, Wallace WA, Al-Nafussi A, Pilling J, Fisher C. Endobronchial pulmonary angiomatoid fibrous histiocytoma: two cases with EWSR1-CREB1 and EWSR1-ATF1 fusions. Am J Surg Pathol. 2012;36:883-8.
65. 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.
66. Wang WL, Mayordomo E, Zhang W, Hernandez VS, Tuvin D, Garcia L, Lev DC, Lazar AJ, López-Terrada D. Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol. 2009;22:1201-9.
67. Antonescu CR. Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD, Ladanyi M. EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2007;46:1051-60.
68. Pacheco M, Horsman DE, Hayes MM, Clarkson PW, Huwait H, Nielsen TO. Small blue round cell tumor of the interosseous membrane bearing a t(2;22)(q34;q12)/EWS-CREB1 translocation: a case report. Mol Cytogenet. 2010;3:12.
69. Debelenko LV, McGregor LM, Shivakumar BR, Dorfman HD, Raimondi SC. A novel EWSR1-CREB3L1 fusion transcript in a case of small cell osteosarcoma. Genes Chromosomes Cancer. 2011;50:1054-62.
70. Batchvarova N, Wang XZ, Ron D. Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153). EMBO J. 1995;14:4654-61.
71. 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.
72. Hosaka T, Nakashima Y, Kusuzaki K, Murata H, Nakayama T, Nakamata T, Aoyama T, Okamoto T, Nishijo K, Araki N, Tsuboyama T, Nakamura T, Toguchida J. A novel type of EWS-CHOP fusion gene in two cases of myxoid liposarcoma. J Mol Diagn. 2002;4:164-71.
73. Modena P, Testi MA, Facchinetti F, Mezzanzanica D, Radice MT, Pilotti S, Sozzi G. UQCRH gene encoding mitochondrial hinge protein is interrupted by a translocation in a soft-tissue sarcoma and epigenetically inactivated in some cancer cell lines. Oncogene. 2003;22:4586-93.
74. Gerlach K, Daniel C, Lehr HA, Nikolaev A, Gerlach T, Atreya R, Rose-John S, Neurath MF, Weigmann B. Transcription factor NFATc2 controls the emergence of colon cancer associated with IL-6-dependent colitis. Cancer Res. 2012;72:4340-50.
75. Baumgart S, Glesel E, Singh G, Chen NM, Reutlinger K, Zhang J, Billadeau DD, Fernandez-Zapico ME, Gress TM, Singh SK, Ellenrieder V. Restricted heterochromatin formation links NFATc2 repressor activity with growth promotion in pancreatic cancer. Gastroenterology. 2012;142:388-98.
76. Perotti V, Baldassari P, Bersani I, Molla A, Vegetti C, Tassi E, Col JD, Dolcetti R, Anichini A, Mortarini R. NFATc2 is a potential therapeutic target in human melanoma. J Invest Dermatol. 2012;132:2652-60.
77. 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.
78. Wang L, Bhargava R, Zheng T, Wexler L, Collins MH, Roulston D, Ladanyi M. 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.
79. Gigek CO, Lisboa LC, Leal MF, Silva PN, Lima EM, Khayat AS, Assumpção PP, Burbano RR, Smith Mde A. SMARCA5 methylation and expression in gastric cancer. Cancer Invest. 2011;29:162-6.
80. Sumegi J, Nishio J, Nelson M, Frayer RW, Perry D, Bridge JA. A novel t(4;22)(q31;q12) produces an EWSR1-SMARCA5 fusion in extraskeletal Ewing sarcoma/primitive neuroectodermal tumor. Mod Pathol. 2011;24:333-42.
81. Meier VS, Kühne T, Jundt G, Gudat F. Molecular diagnosis of Ewing tumors: improved detection of EWS-FLI-1 and EWS-ERG chimeric transcripts and rapid determination of exon combinations. Diagn Mol Pathol. 1998;7:29-35.
82. Kawauchi S, Fukuda T, Miyamoto S, Yoshioka J, Shirahama S, Saito T, Tsukamoto N. Peripheral primitive neuroectodermal tumor of the ovary confirmed by CD99 immunostaining, karyotypic analysis, and RT-PCR for EWS/FLI-1 chimeric mRNA. Am J Surg Pathol. 1998;22:1417-22.
83. Hisaoka M, Tsuji S, Morimitsu Y, Hashimoto H, Shimajiri S, Komiya S, Ushijima M. Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction: application to archival paraffin-embedded tumor tissues. APMIS. 1999;107:577-84.
84. Naito N, Kawai A, Ouchida M, Dan'ura T, Morimoto Y, Ozaki T, Shimizu K, Inoue H. A reverse transcriptase-polymerase chain reaction assay in the diagnosis of soft tissue sarcomas. Cancer. 2000;89:1992-8.
85. Tokudome N, Tanaka K, Kai MH, Sueyoshi K, Matsukita S, Setoguchi T. Primitive neuroectodermal tumor of the transverse colonic mesentery defined by the presence of EWS-FLI1 chimeric mRNA in a Japanese woman. J Gastroenterol. 2002;37:543-9.
86. Stegmaier S, Leuschner I, Aakcha-Rudel E, Münch P, Kazanowska B, Bekassy A, Treuner J, Koscielniak E. Identification of various exon combinations of the ews/fli1 translocation: an optimized RT-PCR method for paraffin embedded tissue a report by the CWS-study group. Klin Padiatr. 2004;216:315-22.
87. Qian X, Jin L, Shearer BM, Ketterling RP, Jalal SM, Lloyd RV. Molecular diagnosis of Ewing's sarcoma/primitive neuroectodermal tumor in formalin-fixed paraffin-embedded tissues by RT-PCR and fluorescence in situ hybridization. Diagn Mol Pathol. 2005;14:23-8.
88. Pellín A, Monteagudo C, López-Ginés C, Carda C, Boix J, Llombart-Bosch A. New type of chimeric fusion product between the EWS and ATFI genes in clear cell sarcoma (malignant melanoma of soft parts). Genes Chromosomes Cancer. 1998;23:358-60.
89. Antonescu CR, Tschernyavsky SJ, Woodruff JM, Jungbluth AA, Brennan MF, Ladanyi M. Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. J Mol Diagn. 2002;4:44-52.
90. Covinsky M, Gong S, Rajaram V, Perry A, Pfeifer J. EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma. Hum Pathol. 2005;36:74-81.
91. Curry CV, Dishop MK, Hicks MJ, Naeem R, Reed JA, López-Terrada DH. Clear cell sarcoma of soft tissue: diagnostic utility of fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction. J Cutan Pathol. 2008;35:411-7.
92. Hamazaki M, Okita H, Hata J, Shimizu S, Kobayashi H, Aoki K, Nara T. Desmoplastic small cell tumor of soft tissue: molecular variant of EWS-WT1 chimeric fusion. Pathol Int. 2006;56:543-8.
93. Gautam U, Srinivasan R, Rajwanshi A, Bansal D, Marwaha RK, Vasishtha RK. Reverse transcriptase-polymerase chain reaction as an ancillary molecular technique in the diagnosis of small blue round cell tumors by fine-needle aspiration cytology. Am J Clin Pathol. 2010;133:633-45.
94. Rougemont AL, Bouron-Dal Soglio D, Patey-Mariaud de Serre N, Fetni R, Fan L, Barrette S, Fournet JC. A t(17;22)(q21;q12) with partial ETV4 deletion in a soft tissue Ewing sarcoma. Cancer Genet. 2012;205:55-60.
95. Lewis TB, Coffin CM, Bernard PS. Differentiating Ewing's sarcoma from other round blue cell tumors using a RT-PCR translocation panel on formalin-fixed paraffin-embedded tissues. Mod Pathol. 2007;20:397-404.
96. Dal Cin P, Sciot R, Panagopoulos I, Aman P, Samson I, Mandahl N. Additional evidence of a variant translocation t(12;22) with EWS/CHOP fusion in myxoid liposarcoma: clinicopathological features. J Pathol. 1997;182:437-41.
97. Matsui Y, Ueda T, Kubo T, Hasegawa T, Tomita Y, Okamoto M. A novel type of EWS-CHOP fusion gene in myxoid liposarcoma. Biochem Biophys Res Commun. 2006;348:437-40.
98. Suzuki K, Matsui Y, Endo K, Kubo T, Hasegawa T, Kimura T. Myxoid liposarcoma with EWS-CHOP type 1 fusion gene. Anticancer Res. 2010;30:4679-83.
99. Bohmann K, Hennig G, Rogel U, Poremba C, Mueller BM, Fritz P. RNA extraction from archival formalin-fixed paraffin-embedded tissue: a comparison of manual, semiautomated, and fully automated purification methods. Clin Chem. 2009;55:1719-27.
100. Botti G, Franco R, Cantile M, Ciliberto G, Ascierto PA. Tumor biobanks in translational medicine. J Transl Med. 2012;10:204.
101. Guo JQ, Lin H, Kantarjian H, Talpaz M, Champlin R, Andreeff M. Comparison of competitive-nested PCR and real-time PCR in detecting BCR-ABL fusion transcripts in chronic myeloid leukemia patients. Leukemia. 2002;16:2447-53.
102. Wattjes MP, Krauter J, Nagel S, Heidenreich O, Ganser A, Heil G. Comparison of nested competitive RT-PCR and real-time RT-PCR for the detection and quantification of AML1/MTG8 fusion transcripts in t(8;21) positive acute myelogenous leukemia. Leukemia. 2000;14:329-35.
103. Bijwaard KE, Fetsch JF, Przygodzki R, Taubenberger JK, Lichy JH. Detection of SYT-SSX fusion transcripts in archival synovial sarcomas by real-time reverse transcriptase-polymerase chain reaction. J Mol Diagn. 2002;4:59-64.
104. Hostein I, Menard A, Bui BN, Lussan C, Wafflart J, Delattre O. Molecular detection of the synovial sarcoma translocation t(X;18) by real-time polymerase chain reaction in paraffin-embedded material. Diagn Mol Pathol. 2002;11:16-21.
105. Nikiforova MN, Groen P, Mutema G, Nikiforov YE, Witte D. Detection of SYT-SSX rearrangements in synovial sarcomas by real-time one-step RT-PCR. Pediatr Dev Pathol. 2005;8:162-7.
106. Wang M, Nilsson G, Carlberg M, Dricu A, Wejde J, Kreicbergs A. Specific and sensitive detection of the EWS/FLI1 fusion protein in Ewing's sarcoma by western blotting. Virchows Arch. 1998;432:131-4.
107. Peng C, Guo W, Yang Y, Zhao H. Downregulation of SS18-SSX1 expression by small interfering RNA inhibits growth and induces apoptosis in human synovial sarcoma cell line HS-SY-II in vitro. Eur J Cancer Prev. 2008;17:392-8.
108. Takenaka S, Naka N, Araki N, Hashimoto N, Ueda T, Yoshioka K. Downregulation of SS18-SSX1 expression in synovial sarcoma by small interfering RNA enhances the focal adhesion pathway and inhibits anchorage-independent growth in vitro and tumor growth in vivo. Int J Oncol. 2010;36:823-31.
109. Oikawa K, Tanaka M, Itoh S, Takanashi M, Ozaki T, Muragaki Y. A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24 expression. Br J Cancer. 2012;106:1976-9.
110. Göransson M, Elias E, Ståhlberg A, Olofsson A, Andersson C, Aman P. Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP beta-mediated interleukin 6 expression. Int J Cancer. 2005;115:556-60.
111. Chansky HA, Barahmand-Pour F, Mei Q, Kahn-Farooqi W, Zielinska- Kwiatkowska A, Blackburn M, Chansky K, Conrad EU 3rd, Bruckner JD, Greenlee TK, Yang L. Targeting of EWS/FLI-1 by RNA interference attenuates the tumor phenotype of Ewing's sarcoma cells in vitro. J Orthop Res. 2004;22:910-7.
112. Prieur A, Tirode F, Cohen P, Delattre O. EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol Cell Biol. 2004;24:7275-83.
113. Hu-Lieskovan S, Heidel JD, Bartlett DW, Davis ME, Triche TJ. Sequence-specific 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.
114. Takigami I, Ohno T, Kitade Y, Hara A, Nagano A, Kawai G, Saitou M, Matsuhashi A, Yamada K, Shimizu K. Synthetic siRNA targeting the breakpoint of EWS/Fli-1 inhibits growth of Ewing sarcoma xenografts in a mouse model. Int J Cancer. 2011;128:216-26.
115. Toub N, Bertrand JR, Malvy C, Fattal E, Couvreur P. Antisense oligonucleotide nanocapsules efficiently inhibit EWS-Fli1 expression in a Ewing's sarcoma model. Oligonucleotides. 2006;16:158-68.
116. Erkizan HV, Kong Y, Merchant M, Schlottmann S, Barber-Rotenberg JS, Yuan L, Abaan OD, Chou TH, Dakshanamurthy S, Brown ML, Uren A, Toretsky JA. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase a inhibits growth of Ewing's sarcoma. Nat Med. 2009;15:750-6.
117. Erkizan HV, Scher LJ, Gamble SE, Barber-Rotenberg JS, Sajwan KP, Üren A, Toretsky JA. Novel peptide binds EWS-FLI1 and reduces the oncogenic potential in Ewing tumors. Cell Cycle. 2011;10:3397-408.
118. Olmos D, Postel-Vinay S, Molife LR, Okuno SH, Schuetze SM, Paccagnella ML, Batzel GN, Yin D, Pritchard-Jones K, Judson I, Worden FP, Gualberto A, Scurr M, de Bono JS, Haluska P. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study. Lancet Oncol. 2010;11:129-35.
119. Surdez D, Benetkiewicz M, Perrin V, Han ZY, Pierron G, Ballet S, Lamoureux F, Rédini F, Decouvelaere AV, Daudigeos-Dubus E, Geoerger B, de Pinieux G, Delattre O, Tirode F. Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes Ewing sarcoma growth. Cancer Res. 2012;72:4494-503.
120. Davis IJ, McFadden AW, Zhang Y, Coxon A, Burgess TL, Wagner AJ, Fisher DE. Identification of the receptor tyrosine kinase c-Met and its ligand, hepatocyte growth factor, as therapeutic targets in clear cell sarcoma. Cancer Res. 2010;70:639-45.