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A common single-nucleotide variant in T is strongly associated with chordoma

Nature Genetics volume 44, pages 1185–1187 (2012)Cite this article

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Abstract

Chordoma is a rare malignant bone tumor that expresses the transcription factor T. We conducted an association study of 40 individuals with chordoma and 358 ancestry-matched controls, with replication in an independent cohort. Whole-exome and Sanger sequencing of T exons showed strong association of the common nonsynonymous SNP rs2305089 with chordoma risk (allelic odds ratio (OR) = 6.1, 95% confidence interval (CI) = 3.1–12.1; P = 4.4 × 10−9), a finding that is exceptional in cancers with a non-Mendelian mode of inheritance.

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Figure 1: Association of rs2305089 with chordoma and T expression.

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References

  1. McMaster, M.L. et al. Cancer Causes Control 12, 1–11 (2001).

    Article  CAS  Google Scholar 

  2. Yang, X.R. et al. Nat. Genet. 41, 1176–1178 (2009).

    Article  CAS  Google Scholar 

  3. Tirabosco, R. et al. Am. J. Surg. Pathol. 32, 572–580 (2008).

    Article  Google Scholar 

  4. Stemple, D.L. Development 132, 2503–2512 (2005).

    Article  CAS  Google Scholar 

  5. Presneau, N. et al. J. Pathol. 223, 327–335 (2011).

    Article  CAS  Google Scholar 

  6. Le, L.P. et al. PLoS ONE 6, e18846 (2011).

    Article  CAS  Google Scholar 

  7. Stephens, P.J. et al. Cell 144, 27–40 (2011).

    Article  CAS  Google Scholar 

  8. Papapetrou, C. et al. FEBS Lett. 409, 201–206 (1997).

    Article  CAS  Google Scholar 

  9. Nelson, A.C. et al. J. Pathol. published, online doi:10.1002/path.4082 (30 July 30 July 2012).

  10. The ENCODE Project Consortium. PLoS Biol. 9, e1001046 (2011).

  11. Tuch, B.B. et al. PLoS ONE 5, e9317 (2010).

    Article  Google Scholar 

  12. Vujovic, S. et al. J. Pathol. 209, 157–165 (2006).

    Article  CAS  Google Scholar 

  13. Easton, D.F. et al. Hum. Mol. Genet. 17, R109–R115 (2008).

    Article  CAS  Google Scholar 

  14. Genin, E. et al. Mol. Psychiatry 16, 903–907 (2011).

    Article  CAS  Google Scholar 

  15. Satagopan, J.M. et al. Cancer Epidemiol. Biomarkers Prev. 10, 467–473 (2001).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to the study subjects for participating in the research and to the clinicians and support staff in the London Sarcoma Service involved in their care. We thank S. McLaren, C. Latimer, K. Raine and A. Butler at the The Wellcome Trust Sanger Institute for assistance with the exome sequencing. We are also grateful to L. Game (Head of Genomics Laboratory, MRC Clinical Sciences Centre) for assistance with aCGH scanning. We are particularly grateful to B. Liegl (Medical University of Graz) for providing us with the chordoma cell line, MUG-Chor1. The research was funded by the Skeletal Cancer Action Trust (SCAT), UK, The Pathological Society (N. Pillay), The Chordoma Foundation, The Rosetrees Foundation and the Wellcome Trust Sanger Institute (grant 98051). The research was part of the RNOH Musculoskeletal Research Programme and Biobank and the UCL Hospital (UCLH)/UCL Comprehensive Biomedical Research Programme and was supported by the UCL Experimental Cancer Centre.

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Authors and Affiliations

  1. Cancer Institute, University College London (UCL), London, UK

    Nischalan Pillay, Nadège Presneau & Adrienne M Flanagan

  2. Histopathology, Royal National Orthopaedic Hospital, Stanmore, UK.,

    Nischalan Pillay, Samira B Lobo, Dina Halai, Fitim Berisha, M Fernanda Amary, Roberto Tirabosco & Adrienne M Flanagan

  3. UCL Genetics Institute, UCL, London, UK

    Vincent Plagnol

  4. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    Patrick S Tarpey

  5. Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands

    Karoly Szuhai

  6. Bone Tumour Unit, Royal National Orthopaedic Hospital, Stanmore, UK

    Stephen R Cannon

  7. Medical Research Council (MRC) Prion Unit, UCL Institute of Neurology, London, UK

    Simon Mead

  8. Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK

    Dalia Kasperaviciute

  9. Cardiovascular Genetics, Institute of Cardiovascular Science, UCL, London, UK.,

    Jutta Palmen & Philippa J Talmud

  10. Department of Histopathology, Royal Orthopaedic Hospital, Birmingham, UK

    Lars-Gunnar Kindblom

Authors
  1. Nischalan Pillay
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  2. Vincent Plagnol
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  3. Patrick S Tarpey
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  4. Samira B Lobo
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  5. Nadège Presneau
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  6. Karoly Szuhai
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  7. Dina Halai
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  8. Fitim Berisha
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  9. Stephen R Cannon
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  10. Simon Mead
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  11. Dalia Kasperaviciute
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  12. Jutta Palmen
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  13. Philippa J Talmud
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  14. Lars-Gunnar Kindblom
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  15. M Fernanda Amary
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  16. Roberto Tirabosco
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  17. Adrienne M Flanagan
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Contributions

N. Pillay and A.M.F. conceived and initiated the project and planned the experiments. V.P. and D.K. performed exome sequencing analysis and SNP6.0 array analysis. N. Pillay, D.H., F.B., P.S.T., S.B.L., N. Presneau, K.S. and J.P. performed the experiments. R.T., M.F.A., A.M.F., L.-G.K., P.J.T., S.M. and S.R.C. selected and provided the samples. N. Pillay, A.M.F. and V.P. wrote the manuscript. All authors reviewed and contributed to the final manuscript.

Corresponding author

Correspondence to Adrienne M Flanagan.

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The authors declare no competing financial interests.

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Supplementary Figures 1–8, Supplementary Tables 1–4 and Supplementary Methods (PDF 1562 kb)

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Pillay, N., Plagnol, V., Tarpey, P. et al. A common single-nucleotide variant in T is strongly associated with chordoma. Nat Genet 44, 1185–1187 (2012). https://doi.org/10.1038/ng.2419

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