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Recurrent PAX3-MAML3 fusion in biphenotypic sinonasal sarcoma

Nature Genetics volume 46, pages 666668 (2014) | Download Citation

Abstract

Biphenotypic sinonasal sarcoma (SNS) is a newly described tumor of the nasal and paranasal areas. Here we report a recurrent chromosomal translocation in SNS, t(2;4)(q35;q31.1), resulting in a PAX3-MAML3 fusion protein that is a potent transcriptional activator of PAX3 response elements. The SNS phenotype is characterized by aberrant expression of genes involved in neuroectodermal and myogenic differentiation, closely simulating the developmental roles of PAX3.

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References

  1. 1.

    et al. Am. J. Surg. Pathol. 36, 517–525 (2012).

  2. 2.

    et al. Nat. Genet. 5, 230–235 (1993).

  3. 3.

    et al. J. Cell. Mol. Med. 12, 2281–2294 (2008).

  4. 4.

    & EMBO J. 12, 2361–2367 (1993).

  5. 5.

    et al. Nature 433, 884–887 (2005).

  6. 6.

    & Crit. Rev. Biochem. Mol. Biol. 44, 85–97 (2009).

  7. 7.

    et al. Dev. Biol. 316, 510–523 (2008).

  8. 8.

    , , & Proc. Natl. Acad. Sci. USA 90, 532–536 (1993).

  9. 9.

    et al. Hum. Mol. Genet. 3, 1069–1074 (1994).

  10. 10.

    , , , & Nature 355, 637–638 (1992).

  11. 11.

    , , & Hum. Mutat. 7, 30–35 (1996).

  12. 12.

    & Dev. Neurobiol. 70, 332–338 (2010).

  13. 13.

    , , , & Nat. Genet. 18, 184–187 (1998).

  14. 14.

    , & Biochem. Biophys. Res. Commun. 411, 832–837 (2011).

  15. 15.

    & Cell. Mol. Life Sci. 68, 1843–1849 (2011).

  16. 16.

    , , , & J. Biol. Chem. 277, 50612–50620 (2002).

  17. 17.

    , & Oncogene 27, 5138–5147 (2008).

  18. 18.

    et al. Nat. Genet. 33, 208–213 (2003).

  19. 19.

    et al. Oncogene (26 August 2013).

  20. 20.

    et al. Cancer Genet. Cytogenet. 145, 139–143 (2003).

  21. 21.

    & Bioinformatics 25, 1754–1760 (2009).

  22. 22.

    et al. Nucleic Acids Res. 39, e100 (2011).

  23. 23.

    et al. Genes Chromosom. Cancer 46, 981–990 (2007).

  24. 24.

    et al. Mol. Cell. Biol. 18, 322–333 (1998).

Download references

Acknowledgements

The authors thank A. Maran, K.L. Shogren, S.L. Segovis, J.L. Herrick and X. Li for logistical support in the performance of several of these experiments. We also express gratitude to L. Jin, M.R. Erickson-Johnson, B.R. Evers, C.W. Roth, R.N. Wehrs, A.R. Seys and M.L. Lonzo for technical support in the Molecular Anatomic Pathology Laboratory and Cytogenetics Laboratory, to T.J. Flotte and L.A. Gross in the Pathology Resource Core Laboratory, to K.C. Halling and M.E. Brown for administration support, to T.L. Schmidt for secretarial assistance and to T.A. Bennett for editorial assistance. We also thank C.P. Kolbert and B.W. Eckloff at the Gene Expression Core and the Sequencing Core at the Mayo Medical Genome Facility for providing transcriptome sequencing and gene expression profiling services. This work was supported by Mayo Clinic DLMP 2012/13 Research Grants and by US National Institutes of Health grant T32 CA148073.

Author information

Author notes

    • Xiaoke Wang
    • , Krista L Bledsoe
    •  & Rondell P Graham

    These authors contributed equally to this work.

Affiliations

  1. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

    • Xiaoke Wang
    • , Rondell P Graham
    • , David S Viswanatha
    • , Jean E Lewis
    • , Jason T Lewis
    •  & André M Oliveira
  2. Department of Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, Minnesota, USA.

    • Krista L Bledsoe
  3. Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA.

    • Yan W Asmann
  4. Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • Margaret M Chou
  5. Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA.

    • Michael J Yaszemski
    • , Jennifer J Westendorf
    •  & André M Oliveira
  6. Medical Genome Facility, Center of Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.

    • Jin Jen

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Contributions

X.W. and K.L.B. performed PCR, qPCR, FISH, cloning experiments, cell culture, luciferase assays, immunoblotting, DNA-binding assays and immunofluorescence experiments. J.E.L., J.T.L., R.P.G. and A.M.O. recognized the disease, reviewed pathology slides and obtained clinical information and tumor material. J.J. provided next-generation sequencing analysis. Y.W.A. performed all bioinformatics analyses. A.M.O., M.J.Y., M.M.C. and D.S.V. reviewed clinical information, performed data analysis and supervised some of the experiments. J.J.W. and A.M.O. planned and supervised the work. All authors contributed to writing the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to André M Oliveira.

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DOI

https://doi.org/10.1038/ng.2989

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