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

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Nature Genetics
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Published online

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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  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


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.

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The authors declare no competing financial interests.

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