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A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS–family transcription factor, ERG

Nature Genetics volume 6, pages 146–151 (1994)Cite this article

Abstract

The t(11;22)(q24;q12), present in 85% of Ewing's sarcoma and related tumours, fuses the EWS gene from chromosome 22q12 and the ETS family member, FLI–1. This results in the expression of a chimaeric protein containing the amino–terminal portion of EWS fused to the ETS DMA–binding domain of FLI–1. We have identified a second Ewing's sarcoma translocation, t(21;22)(q22;q12), that fuses EWS to a different ETS family member, the ERG gene located on band 21q22. Identical EWS nucleotide sequences found in the EWS/FLI–1 fusion transcripts are fused to portions of ERG encoding an ETS DNA–binding domain resulting in expression of a hybrid EWS/ERG protein. These findings suggest that fusion of EWS to different members of the ETS family of transcription factor genes may result in the expression of similar disease phenotypes.

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References

  1. Solomon, E., Borrow, J. & Goddard, A.D. Chromosome aberrations and cancer. Science 254, 1153–1160 (1991).

    Article  CAS  Google Scholar 

  2. Turc-Carel, C., Philip, I., Berger, M.P., Philip, T. & Lenoir, G.M. Chromosomal translocation in Ewing's sarcoma. New Engl. J. Med. 309, 497–498 (1983).

    Google Scholar 

  3. Whang-Peng, J. et al. Chromosome translocation in peripheral neuroepithelioma. New Engl. J. Med. 311, 584–585 (1984).

    Article  CAS  Google Scholar 

  4. Turc-Carel, C. et al. Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12). Cancer Genet. Cytogenet. 32, 229–238 (1988).

    Article  CAS  Google Scholar 

  5. Delattre, O. et al. Cloning of the recurrent t(11;22) translocation of Ewing's sarcoma & peripheral neuroepithelioma. Proc. Am. Assoc. cancer Res. 33, 604–605 (1992).

    Google Scholar 

  6. May, W.A. et al. Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FL11 for transformation. Proc. natn. Acad. Sci. U.S.A. 90, 5752–5756 (1993).

    Article  CAS  Google Scholar 

  7. Sorensen, P.H.B. et al. Reverse transcriptase PCR amplification of EWS/Fli-1 fusion transcripts as a diagnostic test for peripheral primitive neuroectodermal tumours of childhood. Diag. molec. Pathol. 2, 147–157 (1993).

    Article  CAS  Google Scholar 

  8. Ben-David, Y., Giddens, E.B., Letwin, K. & Bernstein, A. Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets family, Fli-1. Genes Dev. 5, 908–918 (1991).

    Article  CAS  Google Scholar 

  9. Prasad, D.D.K., Rao, V.N. & Reddy, E.S.P. Structure and expression of human Fli-1 gene. Cancer Res. 52, 5833–5837 (1992).

    CAS  PubMed  Google Scholar 

  10. Klemsz, M.J., Maki, R.A., Papyannopoulou, T., Moore, J. & Hromas, R. Characterization of the ets oncogene family member, Fli-1. J. biol. Chem. 268, 5769–5773 (1993).

    CAS  PubMed  Google Scholar 

  11. Wasylyk, B., Hahn, S.L. & Giovane, A., The Ets family of transcription factors. Eur. J. Biochem. 211, 7–18 (1993).

    Article  CAS  Google Scholar 

  12. May, W.A. 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 a FLi-1. Molec. Cell. Biol. 13, 7393–7398 (1993).

    Article  CAS  Google Scholar 

  13. Rao, V.N., Papas, T.S. & Reddy, S.P. ERG, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation. Science 237, 635–639 (1987).

    Article  CAS  Google Scholar 

  14. Lautenberger, J.A. et al. Genomic dispersal of the ets gene family during metazoan evolution. Oncogene 7, 1713–1719 (1992).

    CAS  PubMed  Google Scholar 

  15. Wang, C.-Y., Petryniak, B., Ho, I.-C., Thompson, C.B. & Leiden, J.M. Evolutionary conserved Ets family members display distinct DNA binding specificities. J. exp. Med. 175, 1391–1399 (1992).

    Article  CAS  Google Scholar 

  16. Zucman, J. et al. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nature Genet. 4, 341–345 (1993).

    Article  CAS  Google Scholar 

  17. Nourse, J. et al. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 60, 535–545 (1990).

    Article  CAS  Google Scholar 

  18. Kamps, M.P., Murre, C., Sun, X.H. & Baltimore, D. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL Cell 60, 547–555 (1990).

    Article  CAS  Google Scholar 

  19. Inaba, T. et al. Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. Science 257, 531–534 (1992).

    Article  CAS  Google Scholar 

  20. Magrath, I. The pathogenesis of Burkitt's lymphoma. Adv. cancer Res. 55, 133–270 (1990).

    Article  CAS  Google Scholar 

  21. Djabali, M. et al. A trithorax-like gene is interupted by chromosome 11q23 translocations in acute leukemias. Nature Genet. 2, 113–118 (1992).

    Article  CAS  Google Scholar 

  22. Tkachuk, D.C., Kohler, S. & Cleary, M.L. Involvement of a homolog of drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell 71, 691–700 (1992).

    Article  CAS  Google Scholar 

  23. Gu, Y. et al. The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell 71, 701–708 (1992).

    Article  CAS  Google Scholar 

  24. Nakamura, T. et al. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc. natn. Acad. Sci. U.S.A. 90, 4631–1635 (1993).

    Article  CAS  Google Scholar 

  25. Domer, P.H. et al. Acute mixed lineage leukemia t(4;11)(q21;q23) generates a MLL-AF-4 fusion product. Proc. natn. Acad. Sci. U.S.A. 90, 7884–7888 (1993).

    Article  CAS  Google Scholar 

  26. Barch, M.J. The ACT Cytogenetics Laboratory Manual (Raven Press, New York, 1991).

    Google Scholar 

  27. Lichter, P. et al. High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science 247, 64–69 (1990).

    Article  CAS  Google Scholar 

  28. Sambrook, J., Fritch, E.F. & Maniatis, T. Molecular cloning: a laboratory manual. (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  29. Smith, D.B. & Johnson, K.S. Single-step purification of polypeptides in Escherichia coli as fusions with glutathione S-transferase. Gene 67, 31–40 (1988).

    Article  CAS  Google Scholar 

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Author notes

  1. Poul H.B. Sorensen

    Present address: Department of Pathology, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada, V6H 3V4

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Childrens Hospital of Los Angeles/University of Southern California, Los Angeles, California, 90027, USA

    Poul H.B. Sorensen, Dolores Lopez-Terrada, Xian F. Liu & Timothy J. Triche

  2. Department of Molecular Biology Institute and Johnson Comprehensive Cancer Center, Division of Hematohgy, Oncology University of California at Los Angeles, Los Angeles, California, 90024, USA

    Stephen L. Lessnick & Christopher T. Denny

  3. Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, Division of Hematohgy, Oncology University of California at Los Angeles, Los Angeles, California, 90024, USA

    Christopher T. Denny

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  1. Poul H.B. Sorensen
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Sorensen, P., Lessnick, S., Lopez-Terrada, D. et al. A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS–family transcription factor, ERG. Nat Genet 6, 146–151 (1994). https://doi.org/10.1038/ng0294-146

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