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

Behjati, S; Tarpey, PS; Haase, K; Ye, H; Young, MD; Alexandrov, LB; Farndon, SJ; ... Campbell, PJ; + view all (2017) Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma. Nature Communications , 8 , Article 15936. 10.1038/ncomms15936. Green open access

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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.

Type: Article
Title: Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms15936
Publisher version: http://dx.doi.org/10.1038/ncomms15936
Language: English
Additional information: © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, Monoclonal-Antibody, Breast-Cancer, Phase-Ii, Growth, Insulin, Signatures, Sarcoma, Amplification, Combination, Landscape
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/1562188
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