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.

  • Article
  • Published:

Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma

Nature Genetics volume 5, pages 230–235 (1993)Cite this article

A Correction to this article was published on 01 February 1994

Abstract

We have examined the structure and expression of the products associated with the t(2;13)(q35;q14) translocation associated with alveolar rhabdomyosarcoma. The chromosome 13 gene (FKHR) is identified as a member of the fork head domain family of transcription factors characterized by a conserved DNA binding motif. Polymerase chain reaction analysis demonstrates that a 5′ PAX3–3′ FKHR chimaeric transcript is expressed in all eight alveolar rhabdomyosarcomas investigated. Immunoprecipitation experiments detect the predicted fusion protein. These findings indicate that the t(2;13) generates a potentially tumorigenic fusion transcription factor consisting of intact PAX3 DNA binding domains, a truncated fork head DNA binding domain and C–terminal FKHR regions.

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

Similar content being viewed by others

References

  1. Sandberg, A.A. The chromosomes in human cancer and leukemia (Elsevier, New York, 1990).

    Google Scholar 

  2. Delattre, O. et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 359, 162–165 (1992).

    Article  CAS  PubMed  Google Scholar 

  3. Rabbitts, T.H., 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. Nature Genet. 4, 175–180 (1993).

    Article  CAS  PubMed  Google Scholar 

  4. Crozat, A., Aman, P., Mandahl, N. & Ron, D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 363, 640–644 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Barr, F.G. et al. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nature Genet. 3, 113–117 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. Goulding, M.D., Chalepakis, G., Deutsch, U., Erselius, J.R. & Gruss, P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J. 10, 1135–1147 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Weigel, D., Jurgens, G., Kuttner, F., Seifert, E. & Jackle, H. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell 57, 645–658 (1989).

    Article  CAS  PubMed  Google Scholar 

  8. Weigel, D. & Jackle, H. The fork head domain: A novel DNA binding motif of eukaryotic transcription factors?. Cell 63, 455–456 (1990).

    Article  CAS  PubMed  Google Scholar 

  9. Kozak, M. Structural features in eukaryotic tnRNAs that modulate the initiation of translation. J. Biol. Chem. 266, 19867–19870 (1991).

    CAS  PubMed  Google Scholar 

  10. Altschul, S.F. et al. Basic local alignment search tool. J. molec. Biol. 215, 403–410 (1990).

    Article  CAS  PubMed  Google Scholar 

  11. Lai, E. et al. HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. Genes Dev. 4, 1427–1436 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. Li, J. & Vogt, P.K. The retroviral oncogene qin belongs to the transcription factor family that includes the homeotic gene fork head. Proc. natn. Acad. Sci. U.S.A. 90, 4490–4494 (1993).

    Article  CAS  Google Scholar 

  13. Ren, R., Mayer, B.J., Cicchetti, P. & Baltimore, D. Identification of a ten-amino acid proline-rich SH3 binding site. Science 259, 1157–1161 (1993).

    Article  CAS  PubMed  Google Scholar 

  14. Han, K. & Manley, J.L. Transcription repression by the Drosophila Even-skipped protein: definition of a minimal repression domain. Genes Dev. 7, 491–503 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Mitchell, P.J. & Tijan, R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science 245, 371–378 (1989).

    Article  CAS  PubMed  Google Scholar 

  16. Hacker, U., Grossniklaus, U., Gehring, W.J. & Jackle, H. Developmentally regulated Drosophila gene family encoding the fork head domain. Proc. natn. Acad. Sci. U.S.A. 89, 8754–8758 (1992).

    Article  CAS  Google Scholar 

  17. Sasaki, H. & Hogan, B.L.M. Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. Development 118, 47–59 (1993).

    CAS  PubMed  Google Scholar 

  18. Lai, E., Prezioso, V.R., Tao, W., Chen, W.S. & Darnell, J.E. Hepatocyte nuclear factor 3α belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. Genes Dev. 5, 416–427 (1991).

    Article  CAS  PubMed  Google Scholar 

  19. Pani, L. et al. Hepatocyte nuclear factor 3β contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein. Molec. cell. Biol. 12, 3723–3732 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. May, W.A. et al. Ewing sarcoma 11;22 translocation produces a chimaeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc. natn. Acad. Sci. U.S.A. 90, 5752–5756 (1993).

    Article  CAS  Google Scholar 

  21. Clevidence, D.E. et al. Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family. Proc. natn. Acad. Sci. U.S.A. 90, 3948–3952 (1993).

    Article  CAS  Google Scholar 

  22. Maulbecker, C.C. & Gruss, P. The oncogenic potential of Pax genes. EMBO J. 12, 2361–2367 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. MacDonald, R.J., Swift, G.H., Przybyla, A.E. & Chirgwin, J.M. Isolation of RNA using guanidinium salts. Meth. Enzymol. 152, 219–227 (1987).

    Article  CAS  Google Scholar 

  24. Barr, F.G., Holick, J., Nycum, L., Biegel, J.A. & Emanuel, B.S. Localization of the t(2;13) breakpoint of alveolar rhabdomyosarcoma on a physical map of chromosome 2. Genomics 13, 1150–1156 (1992).

    Article  CAS  PubMed  Google Scholar 

  25. Rauscher, F.J. III et al. Fos-associated protein p39 is the product of the jun proto-oncogene. Science 240, 1010–1016 (1988).

    Article  CAS  PubMed  Google Scholar 

  26. Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G. & Noll, M. Conservation of the paired domain in metazoans and its structure in three isolated human genes. EMBO J. 8, 1183–1190 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hoth, C.F. et al. Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I). Am. J. hum. Genet. 52:455–462 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Grossniklaus, U., Pearson, R.K. & Gehring, W.J. The Drosophila sloppy paired locus encodes two proteins involved in segmentation that show homology to mammalian transcription factors. Genes Dev. 6, 1030–1051 (1992).

    Article  CAS  PubMed  Google Scholar 

  29. Tau, W. & Lai, E. Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing brain. Neuron 8, 957–966 (1992).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Wistar Institute, 3601 Spruce St., Philadelphia, Pennsylvania, 19104, USA

    Naomi Galili, William J. Fredericks, Sunil Mukhopadhyay, Frank J. Rauscher III & Giovanni Rovera

  2. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA

    Richard J. Davis & Frederic G. Barr

  3. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA

    Beverly S. Emanuel

Authors
  1. Naomi Galili
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard J. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William J. Fredericks
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunil Mukhopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Frank J. Rauscher III
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beverly S. Emanuel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovanni Rovera
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Frederic G. Barr
    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

Galili, N., Davis, R., Fredericks, W. et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet 5, 230–235 (1993). https://doi.org/10.1038/ng1193-230

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1193-230

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing