Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-06-23

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. More... »

PAGES

15936

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms15936

    DOI

    http://dx.doi.org/10.1038/ncomms15936

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1086127147

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28643781


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