@article{380f1650684141c5961263c7e06841c5,
title = "The driver landscape of sporadic chordoma",
abstract = "Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.",
author = "Tarpey, {Patrick S.} and Sam Behjati and Young, {Matthew D.} and Inigo Martincorena and Alexandrov, {Ludmil B.} and Farndon, {Sarah J.} and Charlotte Guzzo and Claire Hardy and Calli Latimer and Butler, {Adam P.} and Teague, {Jon W.} and Adam Shlien and Futreal, {P. Andrew} and Sohrab Shah and Ali Bashashati and Farzad Jamshidi and Nielsen, {Torsten O.} and David Huntsman and Daniel Baumhoer and Sebastian Brandner and Jay Wunder and Brendan Dickson and Patricia Cogswell and Josh Sommer and Phillips, {Joanna J.} and Amary, {M. Fernanda} and Roberto Tirabosco and Nischalan Pillay and Stephen Yip and Stratton, {Michael R.} and Flanagan, {Adrienne M.} and Campbell, {Peter J.}",
note = "Funding Information: This work was supported by funding from: Wellcome Trust; Skeletal Cancer Action Trust UK; Royal National Orthopaedic Hospital NHS Trust; Rosetrees Trust; Chordoma Foundation USA; Chordoma UK; Terry Fox Research Institute. Support was provided to AMF by the National Institute for Health Research, UCLH Biomedical Research Centre and the UCL Experimental Cancer Centre. Personal fellowships have been granted to S.B. (Wellcome Trust Intermediate Clinical Research Fellowship; St. Baldrick{\textquoteright}s Foundation Robert J. Arceci International Innovation Award), P.J.C. (Wellcome Trust Senior Clinical Research Fellowship), N.P. (CRUK Clinician Scientist Fellowship) and I.M. (CRUK Career Development Fellow). We are grateful for access to samples from the RNOH Stanmore Musculoskeletal Pathology Biobank, from Brain UK and from the UCSF Brain Tumor SPORE Tissue Bank. We thank Clare Unwin, funded by Chordoma UK, for obtaining informed consent from patients and for data collection. We are particularly grateful to the patients for participating in our research and to the clinical teams of the London Sarcoma Service involved in their care. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41467-017-01026-0",
language = "English (US)",
volume = "8",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}