Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma

Tarpey, P. S. et al. (2013) Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma. Nature Genetics, 45(8), pp. 923-926. (doi: 10.1038/ng.2668) (PMID:23770606) (PMCID:PMC3743157)

Abstract

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%).

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cooke, Dr Susie and Martin, Ms Sancha and Marshall, Mr John
• Authors: Tarpey, P. S., Behjati, S., Cooke, S. L., Van Loo, P., Wedge, D. C., Pillay, N., Marshall, J., O'Meara, S., Davies, H., Nik-Zainal, S., Beare, D., Butler, A., Gamble, J., Hardy, C., Hinton, J., Jia, M. M., Jayakumar, A., Jones, D., Latimer, C., Maddison, M., Martin, S., McLaren, S., Menzies, A., Mudie, L., Raine, K., Teague, J. W., Tubio, J. M.C., Halai, D., Tirabosco, R., Amary, F., Campbell, P. J., Stratton, M. R., Flanagan, A. M., and Futreal, P. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 16 June 2013