REFERENCES
1. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. WHO classification of tumours of soft tissue and bone, 4th ed. Lyon, France: IARC Press; 2013.
2. Ewing J. Diffuse endothelioma of bone. Proc N Y Path 1921;21:17-24.
3. Lizard-Nacol S, Lizard G, Justrabo E, Turc-Carel C. Immunologic characterization of Ewing's sarcoma using mesenchymal and neural markers. Am J Pathol 1989;135:847-55.
5. Toomey EC, Schiffman JD, Lessnick SL. Recent advances in the molecular pathogenesis of Ewing's sarcoma. Oncogene 2010;29:4504-16.
6. Geens L, Robays JV, Geert V, der Speeten KV. An unusual location of extraosseous Ewing's sarcoma. Case Rep Oncol 2013;6:293-302.
7. Pizzo PA, Poplack DG. Principles and Practice of Pediatric Oncology, 6th ed. Philadelphia, United States: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2011.
8. Bacci G, Ferrari S, Longhi A, Donati D, De Paolis M, Forni C, Versari M, Setola E, Briccoli A, Barbieri E. Therapy and survival after recurrence of Ewing's tumors: the Rizzoli experience in 195 patients treated with adjuvant and neoadjuvant chemotherapy from 1979 to 1997. Ann Oncol 2003;14:1654-9.
9. Meyers PA, Krailo MD, Ladanyi M, Chan KW, Sailer SL, Dickman PS, Baker DL, Davis JH, Gerbing RB, Grovas A, Herzog CE, Lindsley KL, Liu-Mares W, Nachman JB, Sieger L, Wadman J, Gorlick RG. High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis. J Clin Oncol 2001;19:2812-20.
10. Bernstein M, Kovar H, Paulussen M, Randall RL, Schuck A, Teot LA, Juergens H. Ewing's sarcoma family of tumors: current management. Oncologist 2006;11:503-19.
12. Hamilton SN, Carlson R, Hasan H, Rassekh SR, Goddard K. Long-term outcomes and complications in pediatric Ewing sarcoma. Am J Clin Oncol 2017;40:423-8.
13. Paulussen M, Ahrens S, Burdach S, Craft A, Dockhorn-Dworniczak B, Dunst J, Fröhlich B, Winkelmann W, Zoubek A, Jürgens H. Primary metastatic (stage IV) Ewing tumor: survival analysis of 171 patients from the EICESS studies. European Intergroup Cooperative Ewing Sarcoma Studies. Ann Oncol 1998;9:275-81.
14. Miser JS, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Grier HE. 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. J Clin Oncol 2004;22:2873-6.
15. Drabko K, Raciborska A, Bilska K, Styczynski J, Ussowicz M, Choma M, Wojcik B, Zaucha-Prazmo A, Gorczynska E, Skoczen S, Wozniak W, Chybicka A, Wysocki M, Gozdzik J, Kowalczyk J. Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing's sarcoma. Bone Marrow Transplant 2012;47:1530-4.
16. Ladenstein R, Pötschger U, Le Deley MC, Whelan J, Paulussen M, Oberlin O, van den Berg H, Dirksen U, Hjorth L, Michon J, Lewis I, Craft A, Jürgens H. Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol 2010;28:3284-91.
17. Juergens C, Weston C, Lewis I, Whelan J, Paulussen M, Oberlin O, Michon J, Zoubek A, Juergens H, Craft A. Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. Pediatr Blood Cancer 2006;47:22-9.
18. 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.
19. Zucman J, Melot T, Desmaze C, Ghysdael J, Plougastel B, Peter M, Zucker JM, Triche TJ, Sheer D, Turc-Carel C. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J 1993;12:4481-7.
20. 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.
21. Ohno T, Rao VN, Reddy ES. EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res 1993;53:5859-63.
22. Arvand A, Denny CT. Biology of EWS/ETS fusions in Ewing's family tumors. Oncogene 2001;20:5747-54.
23. Sankar S, Theisen ER, Bearss J, Mulvihill T, Hoffman LM, Sorna V, Beckerle MC, Sharma S, Lessnick SL. Reversible LSD1 inhibition interferes with global EWS/ETS transcriptional activity and impedes Ewing sarcoma tumor growth. Clin Cancer Res 2014;20:4584-97.
24. Tomazou EM, Sheffield NC, Schmidl C, Schuster M, Schönegger A, Datlinger P, Kubicek S, Bock C, Kovar H. Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Rep 2015;10:1082-95.
25. Tanabe Y, Suehara Y, Kohsaka S, Hayashi T, Akaike K, Mukaihara K, Kurihara T, Kim Y, Okubo T, Ishii M, Kazuno S, Kaneko K, Saito T. IRE1α-XBP1 inhibitors exerted anti-tumor activities in Ewing's sarcoma. Oncotarget 2018;9:14428-43.
26. Selvanathan SP, Graham GT, Erkizan HV, Dirksen U, Natarajan TG, Dakic A, Yu S, Liu X, Paulsen MT, Ljungman ME, Wu CH, Lawlor ER, üren A, Toretsky JA. Oncogenic fusion protein EWS-FLI1 is a network hub that regulates alternative splicing. Proc Natl Acad Sci U S A 2015;112:E1307-16.
27. Svoboda LK, Teh SSK, Sud S, Kerk S, Zebolsky A, Treichel S, Thomas D, Halbrook CJ, Lee HJ, Kremer D, Zhang L, Klossowski S, Bankhead AR, Magnuson B, Ljungman M, Cierpicki T, Grembecka J, Lyssiotis CA, Lawlor ER. Menin regulates the serine biosynthetic pathway in Ewing sarcoma. J Pathol 2018; doi: 10.1002/path.5085.
28. Kedage V, Selvaraj N, Nicholas TR, Budka JA, Plotnik JP, Jerde TJ, Hollenhorst PC. An interaction with Ewing's sarcoma breakpoint protein EWS defines a specific oncogenic mechanism of ETS factors rearranged in prostate cancer. Cell Rep 2016;17:1289-301.
29. Lin PP, Brody RI, Hamelin AC, Bradner JE, Healey JH, Ladanyi M. Differential transactivation by alternative EWS-FLI1 fusion proteins correlates with clinical heterogeneity in Ewing's sarcoma. Cancer Res 1999;59:1428-32.
30. de Alava E, Panizo A, Antonescu CR, Huvos AG, Pardo-Mindán FJ, Barr FG, Ladanyi M. Association of EWS-FLI1 type 1 fusion with lower proliferative rate in Ewing's sarcoma. Am J Pathol 2000;156:849-55.
31. Le Deley MC, Delattre O, Schaefer KL, Burchill SA, Koehler G, Hogendoorn PC, Lion T, Poremba C, Marandet J, Ballet S, Pierron G, Brownhill SC, Nesslböck M, Ranft A, Dirksen U, Oberlin O, Lewis IJ, Craft AW, Jürgens H, Kovar H. Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. J Clin Oncol 2010;28:1982-8.
32. Grohar PJ, Kim S, Rangel Rivera GO, Sen N, Haddock S, Harlow ML, Maloney NK, Zhu J, O'Neill M, Jones TL, Huppi K, Grandin M, Gehlhaus K, Klumpp-Thomas CA, Buehler E, Helman LJ, Martin SE, Caplen NJ. Functional genomic screening reveals splicing of the EWS-FLI1 fusion transcript as a vulnerability in Ewing sarcoma. Cell Rep 2016;14:598-610.
33. Minas TZ, Surdez D, Javaheri T, Tanaka M, Howarth M, Kang HJ, Han J, Han ZY, Sax B, Kream BE, Hong SH, Çelik H, Tirode F, Tuckermann J, Toretsky JA, Kenner L, Kovar H, Lee S, Sweet-Cordero EA, Nakamura T, Moriggl R, Delattre O, üren A. Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model. Oncotarget 2017;8:34141-63.
34. Postel-Vinay S, Véron AS, Tirode F, Pierron G, Reynaud S, Kovar H, Oberlin O, Lapouble E, Ballet S, Lucchesi C, Kontny U, González-Neira A, Picci P, Alonso J, Patino-Garcia A, de Paillerets BB, Laud K, Dina C, Froguel P, Clavel-Chapelon F, Doz F, Michon J, Chanock SJ, Thomas G, Cox DG, Delattre O. Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma. Nat Genet 2012;44:323-7.
35. Grünewald TG, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D, Aynaud MM, Mirabeau O, Cidre-Aranaz F, Tirode F, Zaidi S, Perot G, Jonker AH, Lucchesi C, Le Deley MC, Oberlin O, Marec-Bérard P, Véron AS, Reynaud S, Lapouble E, Boeva V, Rio Frio T, Alonso J, Bhatia S, Pierron G, Cancel-Tassin G, Cussenot O, Cox DG, Morton LM, Machiela MJ, Chanock SJ, Charnay P, Delattre O. Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite. Nat Genet 2015;47:1073-8.
36. Gangwal K, Sankar S, Hollenhorst PC, Kinsey M, Haroldsen SC, Shah AA, Boucher KM, Watkins WS, Jorde LB, Graves BJ, Lessnick SL. Microsatellites as EWS/FLI response elements in Ewing's sarcoma. Proc Natl Acad Sci U S A 2008;105:10149-54.
37. 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.
38. Kawamura-Saito M, Yamazaki Y, Kaneko K, Kawaguchi N, Kanda H, Mukai H, Gotoh T, Motoi T, Fukayama M, Aburatani H, Takizawa T, Nakamura T. 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.
39. Pierron G, Tirode F, Lucchesi C, Reynaud S, Ballet S, Cohen-Gogo S, Perrin V, Coindre JM, Delattre O. A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion. Nat Genet 2012;44:461-6.
40. 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.
41. Urano F, Umezawa A, Yabe H, Hong W, Yoshida K, Fujinaga K, Hata J. Molecular analysis of Ewing's sarcoma: another fusion gene, EWS-E1AF, available for diagnosis. Jpn J Cancer Res 1998;89:703-11.
42. 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.
43. Shing DC, McMullan DJ, Roberts P, Smith K, Chin SF, Nicholson J, Tillman RM, Ramani P, Cullinane C, Coleman N. FUS/ERG gene fusions in Ewing's tumors. Cancer Res 2003;63:4568-76.
44. Ng TL, O'Sullivan MJ, Pallen CJ, Hayes M, Clarkson PW, Winstanley M, Sorensen PH, Nielsen TO, Horsman DE. Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn 2007;9:459-63.
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. Brohl AS, Solomon DA, Chang W, Wang J, Song Y, Sindiri S, Patidar R, Hurd L, Chen L, Shern JF, Liao H, Wen X, Gerard J, Kim JS, Lopez Guerrero JA, Machado I, Wai DH, Picci P, Triche T, Horvai AE, Miettinen M, Wei JS, Catchpool D, Llombart-Bosch A, Waldman T, Khan J. The genomic landscape of the Ewing sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet 2014;10:e1004475.
51. Sugita S, Arai Y, Tonooka A, Hama N, Totoki Y, Fujii T, Aoyama T, Asanuma H, Tsukahara T, Kaya M, Shibata T, Hasegawa T. A novel CIC-FOXO4 gene fusion in undifferentiated small round cell sarcoma: a genetically distinct variant of Ewing-like sarcoma. Am J Surg Pathol 2014;38:1571-6.
52. Specht K, Zhang L, Sung YS, Nucci M, Dry S, Vaiyapuri S, Richter GH, Fletcher CD, Antonescu CR. Novel BCOR-MAML3 and ZC3H7B-BCOR gene fusions in undifferentiated small blue round cell sarcomas. Am J Surg Pathol 2016;40:433-42.
53. Alholle A, Karanian M, Brini AT, Morris MR, Kannappan V, Niada S, Niblett A, Ranchère-Vince D, Pissaloux D, Delfour C, Maran-Gonzalez A, Antonescu CR, Sumathi V, Tirode F, Latif F. Genetic analyses of undifferentiated small round cell sarcoma identifies a novel sarcoma subtype with a recurrent CRTC1-SS18 gene fusion. J Pathol 2018;245:186-96.
54. Mugneret F, Lizard S, Aurias A, Turc-Carel C. Chromosomes in Ewing's sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16). Cancer Genet Cytogenet 1988;32:239-45.
55. Armengol G, Tarkkanen M, Virolainen M, Forus A, Valle J, Böhling T, Asko-Seljavaara S, Blomqvist C, Elomaa I, Karaharju E, Kivioja AH, Siimes MA, Tukiainen E, Caballín MR, Myklebost O, Knuutila S. Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization. Br J Cancer 1997;75:1403-9.
56. Maurici D, Perez-Atayde A, Grier HE, Baldini N, Serra M, Fletcher JA. Frequency and implications of chromosome 8 and 12 gains in Ewing sarcoma. Cancer Genet Cytogenet 1998;100:106-10.
57. Hattinger CM, Rumpler S, Ambros IM, Strehl S, Lion T, Zoubek A, Gadner H, Ambros PF. Demonstration of the translocation der(16)t(1;16)(q12;q11.2) in interphase nuclei of Ewing tumors. Genes Chromosomes Cancer 1996;17:141-50.
58. Hattinger CM, Pötschger U, Tarkkanen M, Squire J, Zielenska M, Kiuru-Kuhlefelt S, Kager L, Thorner P, Knuutila S, Niggli FK, Ambros PF, Gadner H, Betts DR. Prognostic impact of chromosomal aberrations in Ewing tumours. Br J Cancer 2002;86:1763-9.
59. Brisset S, Schleiermacher G, Peter M, Mairal A, Oberlin O, Delattre O, Aurias A. CGH analysis of secondary genetic changes in Ewing tumors: correlation with metastatic disease in a series of 43 cases. Cancer Genet Cytogenet 2001;130:57-61.
60. Douglass EC, Rowe ST, Valentine M, Parham D, Meyer WH, Thompson EI. A second nonrandom translocation, der(16)t(1;16)(q21;q13), in Ewing sarcoma and peripheral neuroectodermal tumor. Cytogenet Cell Genet 1990;53:87-90.
61. Sandberg AA, Bridge JA. Updates on cytogenetics and molecular genetics of bone and soft tissue tumors: Ewing sarcoma and peripheral primitive neuroectodermal tumors. Cancer Genet Cytogenet 2000;123:1-26.
62. Mackintosh C, Ordó-ez JL, García-Domínguez DJ, Sevillano V, Llombart-Bosch A, Szuhai K, Scotlandi K, Alberghini M, Sciot R, Sinnaeve F, Hogendoorn PC, Picci P, Knuutila S, Dirksen U, Debiec-Rychter M, Schaefer KL, de álava E. 1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma. Oncogene 2012;31:1287-98.
63. Savola S, Klami A, Tripathi A, Niini T, Serra M, Picci P, Kaski S, Zambelli D, Scotlandi K, Knuutila S. Combined use of expression and CGH arrays pinpoints novel candidate genes in Ewing sarcoma family of tumors. BMC Cancer 2009;9:17.
64. Tirode F, Surdez D, Ma X, Parker M, Le Deley MC, Bahrami A, Zhang Z, Lapouble E, Grossetête-Lalami S, Rusch M, Reynaud S, Rio-Frio T, Hedlund E, Wu G, Chen X, Pierron G, Oberlin O, Zaidi S, Lemmon G, Gupta P, Vadodaria B, Easton J, Gut M, Ding L, Mardis ER, Wilson RK, Shurtleff S, Laurence V, Michon J, Marec-Bérard P, Gut I, Downing J, Dyer M, Zhang J, Delattre O, St. Jude. Children's Research Hospital-Washington University Pediatric Cancer Genome Project and the International Cancer Genome Consortium. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov 2014;4:1342-53.
65. Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC, Calicchio ML, Kiezun A, Carter SL, Shukla SA, Mehta SS, Thorner AR, de Torres C, Lavarino C, Su-ol M, McKenna A, Sivachenko A, Cibulskis K, Lawrence MS, Stojanov P, Rosenberg M, Ambrogio L, Auclair D, Seepo S, Blumenstiel B, DeFelice M, Imaz-Rosshandler I, Schwarz-Cruz Y, Celis A, Rivera MN, Rodriguez-Galindo C, Fleming MD, Golub TR, Getz G, Mora J, Stegmaier K. The genomic landscape of pediatric Ewing sarcoma. Cancer Discov 2014;4:1326-41.
66. Kovar H, Jug G, Aryee DN, Zoubek A, Ambros P, Gruber B, Windhager R, Gadner H. 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 1997;15:2225-32.
67. Tsuchiya T, Sekine K, Hinohara S, Namiki T, Nobori T, Kaneko Y. Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genet Cytogenet 2000;120:91-8.
68. Wei G, Antonescu CR, de Alava E, Leung D, Huvos AG, Meyers PA, Healey JH, Ladanyi M. Prognostic impact of INK4A deletion in Ewing sarcoma. Cancer 2000;89:793-9.
69. Maitra A, Roberts H, Weinberg AG, Geradts J. Aberrant expression of tumor suppressor proteins in the Ewing family of tumors. Arch Pathol Lab Med 2001;125:1207-12.
70. Brownhill SC, Taylor C, Burchill SA. Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT. Br J Cancer 2007;96:1914-23.
71. Honoki K, Stojanovski E, McEvoy M, Fujii H, Tsujiuchi T, Kido A, Takakura Y, Attia J. Prognostic significance of p16 INK4a alteration for Ewing sarcoma: a meta-analysis. Cancer 2007;110:1351-60.
72. Lerman DM, Monument MJ, McIlvaine E, Liu XQ, Huang D, Monovich L, Beeler N, Gorlick RG, Marina NM, Womer RB, Bridge JA, Krailo MD, Randall RL, Lessnick SL; Children's Oncology Group Ewing Sarcoma Biology Committee. Tumoral TP53 and/or CDKN2A alterations are not reliable prognostic biomarkers in patients with localized Ewing sarcoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 2015;62:759-65.
73. Huang HY, Illei PB, Zhao Z, Mazumdar M, Huvos AG, Healey JH, Wexler LH, Gorlick R, Meyers P, Ladanyi M. Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse. J Clin Oncol 2005;23:548-58.
74. Solomon DA, Kim T, Diaz-Martinez LA, Fair J, Elkahloun AG, Harris BT, Toretsky JA, Rosenberg SA, Shukla N, Ladanyi M, Samuels Y, James CD, Yu H, Kim JS, Waldman T. Mutational inactivation of STAG2 causes aneuploidy in human cancer. Science 2011;333:1039-43.
75. Solomon DA, Kim JS, Waldman T. Cohesin gene mutations in tumorigenesis: from discovery to clinical significance. BMB Rep 2014;47:299-310.
76. Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G. Discovery and saturation analysis of cancer genes across 21 tumor types. Nature 2014;505:495-501.
77. Mazumdar C, Shen Y, Xavy S, Zhao F, Reinisch A, Li R, Corces MR, Flynn RA, Buenrostro JD, Chan SM, Thomas D, Koenig JL, Hong WJ, Chang HY, Majeti R. Leukemia-associated cohesin mutants dominantly enforce stem cell programs and impair human hematopoietic progenitor differentiation. Cell Stem Cell 2015;17:675-88.
78. van der Lelij P, Lieb S, Jude J, Wutz G, Santos CP, Falkenberg K, Schlattl A, Ban J, Schwentner R, Hoffmann T, Kovar H, Real FX, Waldman T, Pearson MA, Kraut N, Peters JM, Zuber J, Petronczki M. Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts. Elife 2017;6:e26980.
79. Sheffield NC, Pierron G, Klughammer J, Datlinger P, Schönegger A, Schuster M, Hadler J, Surdez D, Guillemot D, Lapouble E, Freneaux P, Champigneulle J, Bouvier R, Walder D, Ambros IM, Hutter C, Sorz E, Amaral AT, de álava E, Schallmoser K, Strunk D, Rinner B, Liegl-Atzwanger B, Huppertz B, Leithner A, de Pinieux G, Terrier P, Laurence V, Michon J, Ladenstein R, Holter W, Windhager R, Dirksen U, Ambros PF, Delattre O, Kovar H, Bock C, Tomazou EM. DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nat Med 2017;23:386-95.
80. Riggi N, Knoechel B, Gillespie SM, Rheinbay E, Boulay G, Suvà ML, Rossetti NE, Boonseng WE, Oksuz O, Cook EB, Formey A, Patel A, Gymrek M, Thapar V, Deshpande V, Ting DT, Hornicek FJ, Nielsen GP, Stamenkovic I, Aryee MJ, Bernstein BE, Rivera MN. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 2014;26:668-81.
81. Patel N, Black J, Chen X, Marcondes AM, Grady WM, Lawlor ER, Borinstein SC. DNA methylation and gene expression profiling of Ewing sarcoma primary tumors reveal genes that are potential targets of epigenetic inactivation. Sarcoma 2012;2012:498472.
82. Alholle A, Brini AT, Gharanei S, Vaiyapuri S, Arrigoni E, Dallol A, Gentle D, Kishida T, Hiruma T, Avigad S, Grimer R, Maher ER, Latif F. Functional epigenetic approach identifies frequently methylated genes in Ewing sarcoma. Epigenetics 2013;8:1198-204.
83. Huertas-Martínez J, Court F, Rello-Varona S, Herrero-Martín D, Almacellas-Rabaiget O, Sáinz-Jaspeado M, Garcia-Monclús S, Lagares-Tena L, Buj R, Hontecillas-Prieto L, Sastre A, Azorin D, Sanjuan X, López-Alemany R, Moran S, Roma J, Gallego S, Mora J, García Del Muro X, Giangrande PH, Peinado MA, Alonso J, de Alava E, Monk D, Esteller M, Tirado OM. DNA methylation profiling identifies PTRF/Cavin-1 as a novel tumor suppressor in Ewing sarcoma when co-expressed with caveolin-1. Cancer Lett 2017;386:196-207.
84. 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.
85. Lin PP, Pandey MK, Jin F, Xiong S, Deavers M, Parant JM, Lozano G. EWS-FLI1 induces developmental abnormalities and accelerates sarcoma formation in a transgenic mouse model. Cancer Res 2008;68:8968-75.
86. 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.
87. Park H, Galbraith R, Turner T, Mehojah J, Azuma M. Loss of Ewing sarcoma EWS allele promotes tumorigenesis by inducing chromosomal instability in zebrafish. Sci Rep 2016;6:32297.
88. Bacabac RG, Smit TH, Mullender MG, Dijcks SJ, Van Loon JJ, Klein-Nulend J. Nitric oxide production by bone cells is fluid shear stress rate dependent. Biochem Biophys Res Commun 2004;315:823-9.
89. Klein-Nulend J, Bacabac RG, Bakker AD. Mechanical loading and how it affects bone cells: the role of the osteocyte cytoskeleton in maintaining our skeleton. Eur Cell Mater 2012;24:278-91.
90. Santoro M, Lamhamedi-Cherradi SE, Menegaz BA, Ludwig JA, Mikos AG. Flow perfusion effects on three-dimensional culture and drug sensitivity of Ewing sarcoma. Proc Natl Acad Sci U S A 2015;112:10304-9.
91. Santoro M, Menegaz BA, Lamhamedi-Cherradi SE, Molina ER, Wu D, Priebe W, Ludwig JA, Mikos AG. Modeling stroma-induced drug resistance in a tissue-engineered tumor model of Ewing sarcoma. Tissue Eng Part A 2017;23:80-9.
92. Marturano-Kruik A, Villasante A, Yaeger K, Ambati SR, Chramiec A, Raimondi MT, Vunjak-Novakovic G. Biomechanical regulation of drug sensitivity in an engineered model of human tumor. Biomaterials 2018;150:150-61.
93. Scotlandi K, Benini S, Nanni P, Lollini PL, Nicoletti G, Landuzzi L, Serra M, Manara MC, Picci P, Baldini N. Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewing's sarcoma in athymic mice. Cancer Res 1998;58:4127-31.
94. Vormoor J, Baersch G, Decker S, Hotfilder M, Schäfer KL, Pelken L, Rübe C, Van Valen F, Jürgens H, Dockhorn-Dworniczak B. Establishment of an in vivo model for pediatric Ewing tumors by transplantation into NOD/scid mice. Pediatr Res 2001;49:332-41.
95. Franzius C, Hotfilder M, Poremba C, Hermann S, Schäfers K, Gabbert HE, Jürgens H, Schober O, Schäfers M, Vormoor J. Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model. Eur J Nucl Med Mol Imaging 2006;33:1432-41.
96. Wang YX, Mandal D, Wang S, Hughes D, Pollock RE, Lev D, Kleinerman E, Hayes-Jordan A. Inhibiting platelet-derived growth factor β reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model. In Vivo 2009;23:903-9.
97. Vormoor B, Knizia HK, Batey MA, Almeida GS, Wilson I, Dildey P, Sharma A, Blair H, Hide IG, Heidenreich O, Vormoor J, Maxwell RJ, Bacon CM. Development of a preclinical orthotopic xenograft model of Ewing sarcoma and other human malignant bone disease using advanced in vivo imaging. PLoS One 2014;9:e85128.
98. Goldstein SD, Hayashi M, Albert CM, Jackson KW, Loeb DM. An orthotopic xenograft model with survival hindlimb amputation allows investigation of the effect of tumor microenvironment on sarcoma metastasis. Clin Exp Metastasis 2015;32:703-15.
99. Hong SH, Tilan JU, Galli S, Izycka-Swieszewska E, Polk T, Horton M, Mahajan A, Christian D, Jenkins S, Acree R, Connors K, Ledo P, Lu C, Lee YC, Rodriguez O, Toretsky JA, Albanese C, Kitlinska J. High neuropeptide Y release associates with Ewing sarcoma bone dissemination - in vivo model of site-specific metastases. Oncotarget 2015;6:7151-65.
100. Harris JC, Coburn JM, Kajdacsy-Balla A, Kaplan DL, Chiu B. Sustained delivery of vincristine inside an orthotopic mouse sarcoma model decreases tumor growth. J Pediatr Surg 2016;51:2058-62.
101. VAN Noord RA, Thomas T, Krook M, Chukkapalli S, Hoenerhoff MJ, Dillman JR, Lawlor ER, Opipari VP, Newman EA. Tissue-directed implantation using ultrasound visualization for development of biologically relevant metastatic tumor xenografts. In Vivo 2017;31:779-91.
102. Sirsi SR, Flexman ML, Vlachos F, Huang J, Hernandez SL, Kim HK, Johung TB, Gander JW, Reichstein AR, Lampl BS, Wang A, Hielscher AH, Kandel JJ, Yamashiro DJ, Borden MA. Contrast ultrasound imaging for identification of early responder tumor models to anti-angiogenic therapy. Ultrasound Med Biol 2012;38:1019-29.
103. van der Ent W, Jochemsen AG, Teunisse AF, Krens SF, Szuhai K, Spaink HP, Hogendoorn PC, Snaar-Jagalska BE. Ewing sarcoma inhibition by disruption of EWSR1-FLI1 transcriptional activity and reactivation of p53. J Pathol 2014;233:415-24.
104. El-Naggar AM, Veinotte CJ, Cheng H, Grunewald TG, Negri GL, Somasekharan SP, Corkery DP, Tirode F, Mathers J, Khan D, Kyle AH, Baker JH, LePard NE, McKinney S, Hajee S, Bosiljcic M, Leprivier G, Tognon CE, Minchinton AI, Bennewith KL, Delattre O, Wang Y, Dellaire G, Berman JN, Sorensen PH. Translational activation of HIF1α by YB-1 promotes sarcoma metastasis. Cancer Cell 2015;27:682-97.
105. Franzetti GA, Laud-Duval K, van der Ent W, Brisac A, Irondelle M, Aubert S, Dirksen U, Bouvier C, de Pinieux G, Snaar-Jagalska E, Chavrier P, Delattre O. Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells. Oncogene 2017;36:3505-14.
106. Oyama R, Takahashi M, Yoshida A, Sakumoto M, Takai Y, Kito F, Shiozawa K, Qiao Z, Arai Y, Shibata T, Araki Y, Endo M, Kawai A, Kondo T. Generation of novel patient-derived CIC-DUX4 sarcoma xenografts and cell lines. Sci Rep 2017;7:4712.
107. Murakami T, Singh AS, Kiyuna T, Dry SM, Li Y, James AW, Igarashi K, Kawaguchi K, DeLong JC, Zhang Y, Hiroshima Y, Russell T, Eckardt MA, Yanagawa J, Federman N, Matsuyama R, Chishima T, Tanaka K, Bouvet M, Endo I, Eilber FC, Hoffman RM. Effective molecular targeting of CDK4/6 and IGF-1R in a rare FUS-ERG fusion CDKN2A-deletion doxorubicin-resistant Ewing's sarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model. Oncotarget 2016;7:47556-64.
108. TK216 in Patients With Relapsed or Refractory Ewing Sarcoma. ClinicalTrials.gov Identifier: NCT02657005. Available from: https://clinicaltrials.gov/ct2/show/NCT02657005 [Last accessed on 23 May 2018].
109. Gorthi A, Romero JC, Loranc E, Cao L, Lawrence LA, Goodale E, Iniguez AB, Bernard X, Masamsetti VP, Roston S, Lawlor ER, Toretsky JA, Stegmaier K, Lessnick SL, Chen Y, Bishop AJR. EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma. Nature 2018;555:387-91.
110. Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma. ClinicalTrials.gov Identifier: NCT01583543. Available from: https://clinicaltrials.gov/ct2/show/NCT01583543 [Last accessed on 23 May 2018].
111. ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide or Irinotecan in Patients With Previously Treated, Incurable Ewing Sarcoma. ClinicalTrials.gov Identifier: NCT02044120. Available from: https://clinicaltrials.gov/ct2/show/NCT02044120 [Last accessed on 23 May 2018].
112. Kontny HU, Hämmerle K, Klein R, Shayan P, Mackall CL, Niemeyer CM. Sensitivity of Ewing's sarcoma to TRAIL-induced apoptosis. Cell Death Differ 2001;8:506-14.
113. Lissat A, Vraetz T, Tsokos M, Klein R, Braun M, Koutelia N, Fisch P, Romero ME, Long L, Noellke P, Mackall CL, Niemeyer CM, Kontny U. Interferon-gamma sensitizes resistant Ewing's sarcoma cells to tumor necrosis factor apoptosis-inducing ligand-induced apoptosis by up-regulation of caspase-8 without altering chemosensitivity. Am J Pathol 2007;170:1917-30.
114. de Hooge AS, Berghuis D, Santos SJ, Mooiman E, Romeo S, Kummer JA, Egeler RM, van Tol MJ, Melief CJ, Hogendoorn PC, Lankester AC. Expression of cellular FLICE inhibitory protein, caspase-8, and protease inhibitor-9 in Ewing sarcoma and implications for susceptibility to cytotoxic pathways. Clin Cancer Res 2007;13:206-14.
115. Verhoeven DH, de Hooge AS, Mooiman EC, Santos SJ, ten Dam MM, Gelderblom H, Melief CJ, Hogendoorn PC, Egeler RM, van Tol MJ, Schilham MW, Lankester AC. NK cells recognize and lyse Ewing sarcoma cells through NKG2D and DNAM-1 receptor dependent pathways. Mol Immunol 2008;45:3917-25.
116. Pahl JH, Ruslan SE, Kwappenberg KM, van Ostaijen-Ten Dam MM, van Tol MJ, Lankester AC, Schilham MW. Antibody-dependent cell lysis by NK cells is preserved after sarcoma-induced inhibition of NK cell cytotoxicity. Cancer Immunol Immunother 2013;62:1235-47.
117. Guiho R, Biteau K, Grisendi G, Taurelle J, Chatelais M, Gantier M, Heymann D, Dominici M, Redini F. TRAIL delivered by mesenchymal stromal/stem cells counteracts tumor development in orthotopic Ewing sarcoma models. Int J Cancer 2016;139:2802-11.
118. Berghuis D, Santos SJ, Baelde HJ, Taminiau AH, Egeler RM, Schilham MW, Hogendoorn PC, Lankester AC. Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8(+) T-lymphocyte infiltration and affect tumour progression. J Pathol 2011;223:347-57.
119. A Phase I Study of NK Cell Infusion Following Allogeneic Peripheral Blood Stem Cell Transplantation From Related or Matched Unrelated Donors in Pediatric Patients With Solid Tumors and Leukemias. ClinicalTrials.gov Identifier: NCT01287104. Available from: https://clinicaltrials.gov/ct2/show/NCT01287104 [Last accessed on 23 May 2018].
120. Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Sarcomas. ClinicalTrials.gov Identifier: NCT02409576. Available from: https://clinicaltrials.gov/ct2/show/NCT02409576 [Last accessed on 23 May 2018].
121. Phase 2 STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors. ClinicalTrials.gov Identifier: NCT02100891. Available from: https://clinicaltrials.gov/ct2/show/NCT02100891 [Last accessed on 23 May 2018].
122. Haploidentical Stem Cell Transplantation and NK Cell Therapy in Patients With High-risk Solid Tumors. ClinicalTrials.gov Identifier: NCT01807468. Available from: https://clinicaltrials.gov/ct2/show/NCT01807468 [Last accessed on 23 May 2018].
123. Berghuis D, Schilham MW, Vos HI, Santos SJ, Kloess S, Buddingh' EP, Egeler RM, Hogendoorn PC, Lankester AC. Histone deacetylase inhibitors enhance expression of NKG2D ligands in Ewing sarcoma and sensitize for natural killer cell-mediated cytolysis. Clin Sarcoma Res 2012;2:8.
124. Goodison S, Urquidi V. The cancer testis antigen PRAME as a biomarker for solid tumor cancer management. Biomark Med 2012;6:629-32.
125. Osterhoff C, Ivell R, Kirchhoff C. Cloning of a human epididymis-specific mRNA, HE6, encoding a novel member of the seven transmembrane-domain receptor superfamily. DNA Cell Biol 1997;16:379-89.
126. Moreaux J, Kassambara A, Hose D, Klein B. STEAP1 is overexpressed in cancers: a promising therapeutic target. Biochem Biophys Res Commun 2012;429:148-55.
127. Evans CH, Liu F, Porter RM, O'Sullivan RP, Merghoub T, Lunsford EP, Robichaud K, Van Valen F, Lessnick SL, Gebhardt MC, Wells JW. EWS-FLI-1-targeted cytotoxic T-cell killing of multiple tumor types belonging to the Ewing sarcoma family of tumors. Clin Cancer Res 2012;18:5341-51.
128. Berghuis D, de Hooge AS, Santos SJ, Horst D, Wiertz EJ, van Eggermond MC, van den Elsen PJ, Taminiau AH, Ottaviano L, Schaefer KL, Dirksen U, Hooijberg E, Mulder A, Melief CJ, Egeler RM, Schilham MW, Jordanova ES, Hogendoorn PC, Lankester AC. Reduced human leukocyte antigen expression in advanced-stage Ewing sarcoma: implications for immune recognition. J Pathol 2009;218:222-31.
129. Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, Roshal M, Maslak P, Davila M, Brentjens RJ, Sadelain M. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med 2018;378:449-59.
130. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large b-cell lymphoma. N Engl J Med 2017;377:2531-44.
131. Kailayangiri S, Altvater B, Meltzer J, Pscherer S, Luecke A, Dierkes C, Titze U, Leuchte K, Landmeier S, Hotfilder M, Dirksen U, Hardes J, Gosheger G, Juergens H, Rossig C. The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting. Br J Cancer 2012;106:1123-33.
132. Safety and Efficacy Evaluation of 4th Generation Safety-engineered CAR T Cells Targeting Sarcomas. ClinicalTrials.gov Identifier: NCT03356782. Available from: https://clinicaltrials.gov/ct2/show/NCT03356782 [Last accessed on 23 May 2018].
133. Town J, Pais H, Harrison S, Stead LF, Bataille C, Bunjobpol W, Zhang J, Rabbitts TH. Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target. Proc Natl Acad Sci U S A 2016;113:3603-8.
134. Ghisoli M, Barve MA, Schneider R, Mennel RG, Lenarsky C, Wallraven G, Kumar P, Nemunaitis D, Roth A, Senzer NN, Fletcher FA, Nemunaitis JJ. Pilot trial of vigil immunotherapy in Ewing's sarcoma. J Clin Oncol 2015;33 suppl 15:abstr10522.
135. Trial of Bi-shRNA-furin and Granulocyte Macrophage Colony Stimulating Factor (GMCSF) Augmented Autologous Tumor Cell Vaccine for Advanced Cancer. ClinicalTrials.gov Identifier: NCT01061840. Available from: https://clinicaltrials.gov/ct2/show/NCT01061840. [Last accessed on 23 May 2018].
136. Vaccine Therapy and Interleukin-2 in Treating Young Patients With Relapsed or Refractory Ewing's Sarcoma or Neuroblastoma. ClinicalTrials.gov Identifier: NCT00101309. Available from: https://clinicaltrials.gov/ct2/show/NCT00101309. [Last accessed on 23 May 2018].
137. A Two-part Phase IIb Trial of Vigil in Ewing's Sarcoma. ClinicalTrials.gov Identifier: NCT02511132. Available from: https://clinicaltrials.gov/ct2/show/NCT02511132. [Last accessed on 23 May 2018].
138. Vakkila J, Jaffe R, Michelow M, Lotze MT. Pediatric cancers are infiltrated predominantly by macrophages and contain a paucity of dendritic cells: a major nosologic difference with adult tumors. Clin Cancer Res 2006;12:2049-54.