Title |
Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma
|
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Published in |
Nature Communications, June 2017
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DOI | 10.1038/ncomms15936 |
Pubmed ID | |
Authors |
Sam Behjati, Patrick S. Tarpey, Kerstin Haase, Hongtao Ye, Matthew D. Young, Ludmil B. Alexandrov, Sarah J. Farndon, Grace Collord, David C. Wedge, Inigo Martincorena, Susanna L. Cooke, Helen Davies, William Mifsud, Mathias Lidgren, Sancha Martin, Calli Latimer, Mark Maddison, Adam P. Butler, Jon W. Teague, Nischalan Pillay, Adam Shlien, Ultan McDermott, P. Andrew Futreal, Daniel Baumhoer, Olga Zaikova, Bodil Bjerkehagen, Ola Myklebost, M. Fernanda Amary, Roberto Tirabosco, Peter Van Loo, Michael R. Stratton, Adrienne M. Flanagan, Peter J. Campbell |
Abstract |
Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 4 | 27% |
United States | 2 | 13% |
France | 1 | 7% |
Unknown | 8 | 53% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 9 | 60% |
Scientists | 2 | 13% |
Practitioners (doctors, other healthcare professionals) | 2 | 13% |
Science communicators (journalists, bloggers, editors) | 2 | 13% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Netherlands | 1 | <1% |
Unknown | 156 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 37 | 24% |
Student > Ph. D. Student | 24 | 15% |
Student > Master | 21 | 13% |
Student > Bachelor | 13 | 8% |
Student > Doctoral Student | 10 | 6% |
Other | 20 | 13% |
Unknown | 32 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 48 | 31% |
Medicine and Dentistry | 33 | 21% |
Agricultural and Biological Sciences | 19 | 12% |
Computer Science | 4 | 3% |
Immunology and Microbiology | 3 | 2% |
Other | 13 | 8% |
Unknown | 37 | 24% |