Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Biology of EWS/ETS fusions in Ewing's family tumors

Oncogene volume 20, pages 5747–5754 (2001)Cite this article

Abstract

Tumor-associated chromosomal translocations lead to the formation of chimeric fusions between the EWS gene and one of five different ETS transcription factors in Ewing's family tumors (EFTs). The resultant EWS/ETS proteins promote oncogenesis in a dominant fashion in model systems and are necessary for continued growth of EFT cell lines. EWS belongs to a family of genes that encode proteins that may serve as adapters between the RNA polymerase II complex and RNA splicing factors. EWS/ETS fusions have biochemical characteristics of aberrant transcription factors and appear to promote abnormal cellular growth by transcriptionally modulating a network of target genes. Early evidence suggests that EWS/ETS proteins may also impact gene expression through alteration in RNA processing. Elucidation of EWS/ETS target gene networks in the context of other signaling pathways will hopefully lead to biology based therapeutic strategies for EFT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Athanasiou M, Clausen PA, Mavrothalassitis GJ, Zhang XK, Watson DK, Blair DG . 1996 Cell Growth Differ. 7: 1525–1534

  • Attwooll C, Tariq M, Harris M, Coyne JD, Telford N, Varley JM . 1999 Oncogene 18: 7599–7601

  • Aurias A, Rimbaut C, Buffe D, Zucker JM, Mazabraud A . 1984 Cancer Genet. Cytogenet. 12: 21–25

  • Bailly RA, Bosselut R, Zucman J, Cormier F, Delattre O, Roussel M, Thomas G, Ghysdael J . 1994 Mol. Cell. Biol. 14: 3230–3241

  • Bastian LS, Kwiatkowski BA, Breininger J, Danner S, Roth G . 1999 Blood 93: 2637–2644

  • Bertolotti A, Lutz Y, Heard DJ, Chambon P, Tora L . 1996 EMBO J. 15: 5022–5031

  • Bertolotti A, Melot T, Acker J, Vigneron M, Delattre O, Tora L . 1998 Mol. Cell. Biol. 18: 1489–1497

  • Blair DG, Athanasiou M . 2000 Oncogene 19: 6472–6481

  • Brown LA, Rodaway AR, Schilling TF, Jowett T, Ingham PW, Patient RK, Sharrocks AD . 2000 Mech. Dev. 90: 237–252

  • Burchill SA, Wheeldon J, Cullinane C, Lewis IJ . 1997 Eur. J. Cancer 33: 239–243

  • Cavazzana AO, Miser JS, Jefferson J, Triche TJ . 1987 Am. J. Path. 127: 507–518

  • Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS . 1996 Oncogene 12: 229–235

  • Crozat A, Aman P, Mandahl N, Ron D . 1993 Nature (Lond.) 363: 640–644

  • Dalgleish P, Sharrocks AD . 2000 Nucleic Acids Res. 28: 560–569

  • Darby TG, Meissner JD, Ruhlmann A, Mueller WH, Scheibe RJ . 1997 Oncogene 15: 3067–3082

  • de Alava E, Kawai A, Healey JH, Fligman I, Meyers PA, Huvos AG, Gerald WL, Jhanwar SC, Argani P, Antonescu CR, Pardo-Mindan FJ, Ginsberg J, Womer R, Lawlor ER, Wunder J, Andrulis I, Sorensen PH, Barr FG, Ladanyi M . 1998 J. Clin. Oncol. 16: 1248–1255

  • Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, Ambros PF, Sheer D, Turc-Carel C, Triche TJ, Aurias A, Thomas G . 1994 N. Engl. J. Med. 331: 294–299

  • Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, Aurias A, Thomas G . 1992 Nature 359: 162–165

  • Deloulme JC, Prichard L, Delattre O, Storm DR . 1997 J. Biol. Chem. 272: 27369–27377

  • Deveaux S, Filipe A, Lemarchandel V, Ghysdael J, Roméo PH, Mignotte V . 1996 Blood 87: 4678–4685

  • Dhulipala PD, Lee L, Rao VN, Reddy ES . 1998 Oncogene 17: 1149–1157

  • Felsch JS, Lane WS, Peralta EG . 1999 Curr. Biol. 9: 485–488

  • Fitzsimmons D, Hodsdon W, Wheat W, Maira SM, Wasylyk B, Hagman J . 1996 Genes Dev. 10: 2198–2211

  • Graves BJ, Petersen JM . 1998 Adv. Cancer Res. 75: 1–55

  • Guinamard R, Fougereau M, Seckinger P . 1997 Scand. J. Immunol. 45: 587–595

  • Hahm KB . 1999 Nat. Genet. 23: 481

  • Hallier M, Lerga A, Barnache S, Tavitian A, Moreau-Gachelin F . 1998 J. Biol. Chem. 273: 4838–4842

  • Hart A, Melet F, Grossfeld P, Chien K, Jones C, Tunnacliffe A, Favier R, Bernstein A . 2000 Immunity 13: 167–177

  • Hicks GG, Singh N, Nashabi A, Mai S, Bozek G, Klewes L, Arapovic D, White EK, Koury MJ, Oltz EM, Van Kaer L, Ruley HE . 2000 Nature Genet. 24: 175–179

  • Ichikawa H, Shimizu K, Hayashi Y, Ohki M . 1994 Cancer Res. 54: 2865–2868

  • Im YH, Kim HT, Lee C, Poulin D, Welford S, Sorensen PH, Denny CT, Kim SJ . 2000 Cancer Res. 60: 1536–1540

  • Immanuel D, Zinszner H, Ron D . 1995 Mol. Cell. Biol. 15: 4562–4571

  • Jaishankar S, Zhang J, Roussel MF, Baker SJ . 1999 Oncogene 18: 5592–5597

  • Javelaud D, Wietzerbin J, Delattre O, Besancon F . 2000 Oncogene 19: 61–68

  • Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN . 1995 Oncogene 10: 1229–1234

  • Kaneko Y, Yoshida K, Handa M, Toyoda Y, Nishihira H, Tanaka Y, Sasaki Y, Ishida S, Higashino F, Fujinaga K . 1996 Genes, Chrom. Cancer 15: 115–121

  • Knoop LL, Baker SJ . 2000 J. Biol. Chem. 275: 24865–24871

  • Kontny HU, Lehrnbecher TM, Chanock SJ, Mackall CL . 1998 Cancer Res. 58: 5842–5849

  • Kovar H, Aryee DN, Jug G, Henockl C, Schemper M, Delattre O, Thomas G, Gadner H . 1996 Cell Growth Differ. 7: 429–437

  • Kovar H, Dworzak M, Strehl S, Schnell E, Ambros IM, Ambros PF, Gadner H . 1990 Oncogene 5: 1067–10670

  • Kovar H, Jug G, Aryee DN, Zoubek A, Ambros P, Gruber B, Windhager R, Gadner H . 1997 Oncogene 15: 2225–2232

  • Kuroda M, Sok J, Webb L, Baechtold H, Urano F, Yin Y, Chung P, de Rooij DG, Akhmedov A, Ashley T, Ron D . 2000 EMBO J. 19: 453–462

  • Kwiatkowski BA, Bastian LS, Bauer TR, Tsai S, Zielinska-Kwiatkowska AG, Hickstein DD . 1998 J. Biol. Chem. 273: 17525–17530

  • Kwiatkowski BA, Zielinska-Kwiatkowska AG, Bauer TR, Hickstein DD . 2000 Blood Cells Mol. Dis. 26: 84–90

  • Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M, Aurias A, Delattre O, Thomas G . 1995 Hum. Mol. Gen. 4: 2219–2226

  • Ladanyi M, Gerald W . 1994 Cancer Res. 54: 2837–2840

  • Lambert G, Bertrand JR, Fattal E, Subra F, Pinto-Alphandary H, Malvy C, Auclair C, Couvreur P . 2000 Biochem. Biophys. Res. Commun. 279: 401–406

  • Lessnick SL, Braun BS, Denny CT, May WA . 1995 Oncogene 10: 423–431

  • Li R, Huiping P, Watson DK . 2000 Oncogene 19: 6514–6523

  • Mager AM, Grapin-Botton A, Ladjali K, Meyer D, Wolff CM, Stiegler P, Bonnin MA, Remy P . 1998 Int. J. Dev. Biol. 42: 561–572

  • Magnaghi-Jaulin L, Masutani H, Robin P, Lipinski M, Harel-Bellan A . 1996 Nucleic Acids Res. 24: 1052–1058

  • Mao X, Miesfeldt S, Yang H, Leiden JM, Thompson CB . 1994 J. Biol. Chem. 269: 18216–18222

  • Maroulakou IG, Bowe DB . 2000 Oncogene 19: 6432–6442

  • Mastrangelo T, Modena P, Tornielli S, Bullrich F, Testi MA, Mezzelani A, Radice P, Azzarelli A, Pilotti S, Croce CM, Pierotti MA, Sozzi G . 2000 Oncogene 19: 3799–3804

  • May WA, Arvand A, Thompson AD, Braun BS, Wright M, Denny CT . 1997 Nat. Genet. 17: 495–497

  • May WA, Gishizky ML, Lessnick SL, Lunsford LB, Lewis BC, Delattre O, Zucman J, Thomas G, Denny CT . 1993a Proc. Natl. Acad. Sci. USA 90: 5752–5756

  • May WA, Lessnick SL, Braun BS, Klemsz M, Lewis BC, Lunsford LB, Hromas R, Denny CT . 1993b Mol. Cell. Biol. 13: 7393–7398

  • Mélet F, Motro B, Rossi DJ, Zhang L, Bernstein A . 1996 Mol. Cell. Biol. 16: 2708–2718

  • Meyer D, Wolff CM, Stiegler P, Senan F, Befort N, Befort JJ, Remy P . 1993 Mech. Dev. 44: 109–121

  • Mitsiades N, Poulaki V, Leone A, Tsokos M . 1999 J. Natl. Cancer Inst. 91: 1678–1684

  • Morrison SJ, White PM, Zock C, Anderson DJ . 1999 Cell 96: 737–749

  • Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN, Reddy ES . 1994 Oncogene 9: 3087–3097

  • Ohno T, Rao VN, Reddy ES . 1993 Cancer Res. 53: 5859–5863

  • Ouchida M, Ohno T, Fujimura Y, Rao VN, Reddy ES . 1995 Oncogene 11: 1049–1054

  • Panagopoulos I, Hoglund M, Mertens F, Mandahl N, Mitelman F, Aman P . 1996 Oncogene 12: 489–494

  • Pereira R, Quang CT, Lesault I, Dolznig H, Beug H, Ghysdael J . 1999 Oncogene 18: 1597–1608

  • Perrotti D, Bonatti S, Trotta R, Martinez R, Skorski T, Salomoni P, Grassilli E, Lozzo RV, Cooper DR, Calabretta B . 1998 EMBO J. 17: 4442–4455

  • Perrotti D, Iervolino A, Cesi V, Cirinna M, Lombardini S, Grassilli E, Bonatti S, Claudio PP, Calabretta B . 2000 Mol. Cell. Biol. 20: 6159–6169

  • Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H, Delattre O . 1997 Oncogene 14: 1159–1164

  • Petermann R, Mossier BM, Aryee DN, Khazak V, Golemis EA, Kovar H . 1998 Oncogene 17: 603–610

  • Powers CA, Mathur M, Raaka BM, Ron D, Samuels HH . 1998 Mol. Endocrin. 12: 4–18

  • Prasad DD, Ouchida M, Lee L, Rao VN, Reddy ES . 1994 Oncogene 9: 3717–3729

  • Rabbitts TH, Forster A, Larson R, Nathan P . 1993 Nature Gen. 4: 175–180

  • Rao VN, Ohno T, Prasad DD, Bhattacharya G, Reddy ES . 1993 Oncogene 8: 2167–2173

  • Rauscher FJ, Benjamin LE, Fredericks WJ, Morris JF . 1994 Cold Spring Harb. Symp. Quant. Biol. 59: 137–146

  • Sancéau J, Hiscott J, Delattre O, Wietzerbin J . 2000 Oncogene 19: 3372–3383

  • Sarrazin S, Starck J, Gonnet C, Doubeikovski A, Melet F, Morle F . 2000 Mol. Cell. Biol. 20: 2959–2969

  • Scotlandi K, Baldini N, Cerisano V, Manara MC, Benini S, Serra M, Lollini PL, Nanni P, Nicoletti G, Bernard G, Bernard A, Picci P . 2000a Cancer Res. 60: 5134–5142

  • Scotlandi K, Chano T, Benini S, Serra M, Manara MC, Cerisano V, Picci P, Baldini N . 2000b Intl. J. Cancer 87: 328–335

  • Sjögren H, Meis-Kindblom J, Kindblom LG, Aman P, Stenman G . 1999 Cancer Res. 59: 5064–5067

  • Sohn HW, Choi EY, Kim SH, Lee IS, Chung DH, Sung UA, Hwang DH, Cho SS, Jun BH, Jang JJ, Chi JG, Park SH . 1998 Am. J. Path. 153: 1937–1945

  • Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT . 1994 Nat. Genet. 6: 146–151

  • Sorensen PH, Shimada H, Liu XF, Lim JF, Thomas G, Triche TJ . 1995 Cancer Res. 55: 1385–1392

  • Spyropoulos DD, Pharr PN, Lavenburg KR, Jackers P, Papas TS, Ogawa M, Watson DK . 2000 Mol. Cell. Biol. 20: 5643–5652

  • Stolow DT, Haynes SR . 1995 Nucleic Acids Res. 23: 835–843

  • Tamir A, Howard J, Higgins RR, Li YJ, Berger L, Zacksenhaus E, Reis M, Ben-David Y . 1999 Mol. Cell. Biol. 19: 4452–4464

  • Tanaka K, Iwakuma T, Harimaya K, Sato H, Iwamoto Y . 1997 J. Clin. Invest. 99: 239–247

  • Teitell MA, Thompson AD, Sorensen PH, Shimada H, Triche TJ, Denny CT . 1999 Lab. Invest. 79: 1535–1543

  • Thompson AD, Teitell MA, Arvand A, Denny CT . 1999 Oncogene 18: 5506–5513

  • Thorner P, Squire J, Chilton-MacNeil S, Marrano P, Bayani J, Malkin D, Greenberg M, Lorenzana A, Zielenska M . 1996 Am. J. Pathol. 148: 1125–1138

  • Triche TJ, Askin FB, Kissane JM . 1987 Major Problems in Pathology Vol. 18. Feingold M. and Bennington JC (eds) Saunders: Philadelphia pp. 145–195

    Google Scholar 

  • Truong AHL, Ben-David Y . 2000 Oncogene 19: 6482–6489

  • Turc-Carel C, Philip I, Berger MP, Philip T, Lenoir GM . 1984 Cancer Gen. Cytogen. 12: 1–19

  • Urano F, Umezawa A, Hong W, Kikuchi H, Hata J . 1996 Biochem. Biophys. Res. Commun. 219: 608–612

  • Watson DK, Robinson L, Hodge DR, Kola I, Papas TS, Seth A . 1997 Oncogene 14: 213–221

  • Watson DK, Seth A . 2000 Oncogene 55: 6393–6547

  • Wei G, Antonescu CR, de Alava E, Leung D, Huvos AG, Meyers PA, Healey JH, Ladanyi M . 2000 Cancer 89: 793–799

  • Yang L, Chansky HA, Hickstein DD . 2000a J. Biol. Chem. 275: 37612–37618

  • Yang L, Embree LJ, Hickstein DD . 2000b Mol. Cell. Biol. 20: 3345–3354

  • Yang L, Embree LJ, Tsai S, Hickstein DD . 1998 J. Biol. Chem. 273: 27761–27764

  • Zhang L, Eddy A, Teng YT, Fritzler M, Kluppel M, Melet F, Bernstein A . 1995 Mol. Cell. Biol. 15: 6961–6970

  • Zinszner H, Albalat R, Ron D . 1994 Genes Dev. 8: 2513–2526

  • Zinszner H, Sok J, Immanuel D, Yin Y, Ron D . 1997 J. Cell. Sci. 110: 1741–1750

  • Zoubek A, Dockhorn-Dworniczak B, Delattre O, Christiansen H, Niggli F, Gatterer-Menz I, Smith TL, Jurgens H, Gadner H, Kovar H . 1996 J. Clin. Oncol. 14: 1245–1251

  • Zoubek A, Pfleiderer C, Salzer-Kuntschik M, Amann G, Windhager R, Fink FM, Koscielniak E, Delattre O, Strehl S, Ambros PF, Gadner H, Kovar H . 1994 Br. J. Cancer 70: 908–913

  • Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, Fletchers CD, Aurias A, Thomas G . 1993a Nature Gen. 4: 341–345

  • Zucman J, Melot T, Desmaze C, Ghysdael J, Plougastel B, Peter M, Zucker JM, Triche TJ, Sheer D, Turc-Carel C, Ambros P, Combaret V, Lenoir G, Aurias A, Thomas G, Delattre O . 1993b EMBO J. 12: 4481–4487

  • Zwerner JP, May WA . 2001 Oncogene 20: 626–633

Download references

Acknowledgements

This work is supported through the National Institutes of Health grant RO1-87771.

Author information

Authors and Affiliations

  1. Molecular Biology Institute, Gwynne Hazen Cherry Memorial Labs, University of California at Los Angeles, California, USA

    Christopher T Denny

  2. Jonsson Comprehensive Cancer, Gwynne Hazen Cherry Memorial Labs, University of California at Los Angeles, California, USA

    Christopher T Denny

  3. Department of Pathology and Laboratory Medicine, Gwynne Hazen Cherry Memorial Labs, University of California at Los Angeles, California, USA

    Afsane Arvand

  4. Department of Pediatrics, Gwynne Hazen Cherry Memorial Labs, University of California at Los Angeles, California, USA

    Christopher T Denny

Authors
  1. Afsane Arvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher T Denny
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arvand, A., Denny, C. Biology of EWS/ETS fusions in Ewing's family tumors. Oncogene 20, 5747–5754 (2001). https://doi.org/10.1038/sj.onc.1204598

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204598

Keywords

This article is cited by

Search

Advanced search

Quick links