Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central chondrosarcomas. However, there has been little systematic genomic analysis of this tumor type, and, thus, the contribution of other genes is unclear. Here we report comprehensive genomic analyses of 49 individuals with chondrosarcoma (cases). We identified hypermutability of the major cartilage collagen gene COL2A1, with insertions, deletions and rearrangements identified in 37% of cases. The patterns of mutation were consistent with selection for variants likely to impair normal collagen biosynthesis. In addition, we identified mutations in IDH1 or IDH2 (59%), TP53 (20%), the RB1 pathway (33%) and Hedgehog signaling (18%).

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We are grateful to the patients for participating in the research and to the clinicians and support staff of the London Sarcoma Service involved in their care. This work was supported by funding from the Wellcome Trust (grant 077012/Z/05/Z) and the Skeletal Cancer Action Trust (SCAT), UK. Material was obtained from the Royal National Orthopaedic Hospital Musculoskeletal Research Program and Biobank. Support was provided to A.M.F. by the National Institute for Health Research, the University College London Hospital Biomedical Research Centre and the UCL Experimental Cancer Centre. P.J.C. is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant WT088340MA). P.V.L. is a postdoctoral researcher of the Research Foundation–Flanders (FWO). S.B. is funded through the Wellcome Trust PhD Programme for Clinicians.

Author information

Author notes

    • Patrick S Tarpey
    •  & Sam Behjati

    These authors contributed equally to this work.


  1. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Patrick S Tarpey
    • , Sam Behjati
    • , Susanna L Cooke
    • , Peter Van Loo
    • , David C Wedge
    • , John Marshall
    • , Sarah O'Meara
    • , Helen Davies
    • , Serena Nik-Zainal
    • , David Beare
    • , Adam Butler
    • , John Gamble
    • , Claire Hardy
    • , Jonathon Hinton
    • , Ming Ming Jia
    • , Alagu Jayakumar
    • , David Jones
    • , Calli Latimer
    • , Mark Maddison
    • , Sancha Martin
    • , Stuart McLaren
    • , Andrew Menzies
    • , Laura Mudie
    • , Keiran Raine
    • , Jon W Teague
    • , Jose M C Tubio
    • , Peter J Campbell
    • , Michael R Stratton
    •  & P Andrew Futreal
  2. Department of Paediatrics, University of Cambridge, Cambridge, UK.

    • Sam Behjati
  3. Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, Leuven, Belgium.

    • Peter Van Loo
  4. Histopathology, Royal National Orthopaedic Hospital National Health Service (NHS) Trust, Stanmore, UK.

    • Nischalan Pillay
    • , Dina Halai
    • , Roberto Tirabosco
    • , Fernanda Amary
    •  & Adrienne M Flanagan
  5. University College London (UCL) Cancer Institute, London, UK.

    • Nischalan Pillay
    •  & Adrienne M Flanagan
  6. Department of Haematology, Addenbrooke's Hospital, Cambridge, UK.

    • Peter J Campbell
  7. Department of Haematology, University of Cambridge, Cambridge, UK.

    • Peter J Campbell


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P.S.T. and S.B. analyzed the sequence data. S.L.C. and J.M.C.T. performed rearrangement analysis. P.V.L. analyzed the SNP6 array data. D.C.W. performed statistical analyses. S. McLaren, D.H. and S.O. coordinated sample processing and technical investigations. S. Martin coordinated sample acquisition and processing. C.H., C.L., L.M. and M.M. performed technical investigations. A.B., J.G., J.H., M.M.J., A.J., D.J., A.M., J.M., K.R., J.W.T., H.D., S.N.-Z. and D.B. performed informatic investigations. F.A., R.T., N.P. and A.M.F. provided samples and clinical data and performed immunohistochemistry. P.J.C., M.R.S., A.M.F. and P.A.F. directed the research and contributed to the manuscript. P.A.F. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to P Andrew Futreal.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–5, Supplementary Tables 1 and 3–6

Excel files

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    Supplementary Table 2

    Variants identified in the primary whole exome screen and in the extension series (Excel file)

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    Supplementary Table 7

    Copy number changes identified in 49 chondrosarcomas (Excel file)

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