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The driver landscape of sporadic chordoma
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 recapi...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2017
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638846/ https://www.ncbi.nlm.nih.gov/pubmed/29026114 http://dx.doi.org/10.1038/s41467-017-01026-0 |
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| author | Tarpey, Patrick S. Behjati, Sam Young, Matthew D. Martincorena, Inigo Alexandrov, Ludmil B. Farndon, Sarah J. Guzzo, Charlotte Hardy, Claire Latimer, Calli Butler, Adam P. Teague, Jon W. Shlien, Adam Futreal, P. Andrew Shah, Sohrab Bashashati, Ali Jamshidi, Farzad Nielsen, Torsten O. Huntsman, David Baumhoer, Daniel Brandner, Sebastian Wunder, Jay Dickson, Brendan Cogswell, Patricia Sommer, Josh Phillips, Joanna J. Amary, M. Fernanda Tirabosco, Roberto Pillay, Nischalan Yip, Stephen Stratton, Michael R. Flanagan, Adrienne M. Campbell, Peter J. |
| author_facet | Tarpey, Patrick S. Behjati, Sam Young, Matthew D. Martincorena, Inigo Alexandrov, Ludmil B. Farndon, Sarah J. Guzzo, Charlotte Hardy, Claire Latimer, Calli Butler, Adam P. Teague, Jon W. Shlien, Adam Futreal, P. Andrew Shah, Sohrab Bashashati, Ali Jamshidi, Farzad Nielsen, Torsten O. Huntsman, David Baumhoer, Daniel Brandner, Sebastian Wunder, Jay Dickson, Brendan Cogswell, Patricia Sommer, Josh Phillips, Joanna J. Amary, M. Fernanda Tirabosco, Roberto Pillay, Nischalan Yip, Stephen Stratton, Michael R. Flanagan, Adrienne M. Campbell, Peter J. |
| author_sort | Tarpey, Patrick S. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-5638846 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2017 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-56388462017-10-17 The driver landscape of sporadic chordoma Tarpey, Patrick S. Behjati, Sam Young, Matthew D. Martincorena, Inigo Alexandrov, Ludmil B. Farndon, Sarah J. Guzzo, Charlotte Hardy, Claire Latimer, Calli Butler, Adam P. Teague, Jon W. Shlien, Adam Futreal, P. Andrew Shah, Sohrab Bashashati, Ali Jamshidi, Farzad Nielsen, Torsten O. Huntsman, David Baumhoer, Daniel Brandner, Sebastian Wunder, Jay Dickson, Brendan Cogswell, Patricia Sommer, Josh Phillips, Joanna J. Amary, M. Fernanda Tirabosco, Roberto Pillay, Nischalan Yip, Stephen Stratton, Michael R. Flanagan, Adrienne M. Campbell, Peter J. Nat Commun Article 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. Nature Publishing Group UK 2017-10-12 /pmc/articles/PMC5638846/ /pubmed/29026114 http://dx.doi.org/10.1038/s41467-017-01026-0 Text en © The Author(s) 2017 Open Access 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/. |
| spellingShingle | Article Tarpey, Patrick S. Behjati, Sam Young, Matthew D. Martincorena, Inigo Alexandrov, Ludmil B. Farndon, Sarah J. Guzzo, Charlotte Hardy, Claire Latimer, Calli Butler, Adam P. Teague, Jon W. Shlien, Adam Futreal, P. Andrew Shah, Sohrab Bashashati, Ali Jamshidi, Farzad Nielsen, Torsten O. Huntsman, David Baumhoer, Daniel Brandner, Sebastian Wunder, Jay Dickson, Brendan Cogswell, Patricia Sommer, Josh Phillips, Joanna J. Amary, M. Fernanda Tirabosco, Roberto Pillay, Nischalan Yip, Stephen Stratton, Michael R. Flanagan, Adrienne M. Campbell, Peter J. The driver landscape of sporadic chordoma |
| title | The driver landscape of sporadic chordoma |
| title_full | The driver landscape of sporadic chordoma |
| title_fullStr | The driver landscape of sporadic chordoma |
| title_full_unstemmed | The driver landscape of sporadic chordoma |
| title_short | The driver landscape of sporadic chordoma |
| title_sort | driver landscape of sporadic chordoma |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638846/ https://www.ncbi.nlm.nih.gov/pubmed/29026114 http://dx.doi.org/10.1038/s41467-017-01026-0 |
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