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Copy-number signatures and mutational processes in ovarian carcinoma
The genomic complexity of profound copy-number aberration has prevented effective molecular stratification of ovarian cancers. To decode this complexity, we derived copy-number signatures from shallow whole genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130818/ https://www.ncbi.nlm.nih.gov/pubmed/30104763 http://dx.doi.org/10.1038/s41588-018-0179-8 |
| _version_ | 1783354013001973760 |
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| author | Macintyre, Geoff Goranova, Teodora E. De Silva, Dilrini Ennis, Darren Piskorz, Anna M. Eldridge, Matthew Sie, Daoud Lewsley, Liz-Anne Hanif, Aishah Wilson, Cheryl Dowson, Suzanne Glasspool, Rosalind M. Lockley, Michelle Brockbank, Elly Montes, Ana Walther, Axel Sundar, Sudha Edmondson, Richard Hall, Geoff D. Clamp, Andrew Gourley, Charlie Hall, Marcia Fotopoulou, Christina Gabra, Hani Paul, James Supernat, Anna Millan, David Hoyle, Aoisha Bryson, Gareth Nourse, Craig Mincarelli, Laura Navarro Sanchez, Luis Ylstra, Bauke Jimenez-Linan, Mercedes Moore, Luiza Hofmann, Oliver Markowetz, Florian McNeish, Iain A. Brenton, James D. |
| author_facet | Macintyre, Geoff Goranova, Teodora E. De Silva, Dilrini Ennis, Darren Piskorz, Anna M. Eldridge, Matthew Sie, Daoud Lewsley, Liz-Anne Hanif, Aishah Wilson, Cheryl Dowson, Suzanne Glasspool, Rosalind M. Lockley, Michelle Brockbank, Elly Montes, Ana Walther, Axel Sundar, Sudha Edmondson, Richard Hall, Geoff D. Clamp, Andrew Gourley, Charlie Hall, Marcia Fotopoulou, Christina Gabra, Hani Paul, James Supernat, Anna Millan, David Hoyle, Aoisha Bryson, Gareth Nourse, Craig Mincarelli, Laura Navarro Sanchez, Luis Ylstra, Bauke Jimenez-Linan, Mercedes Moore, Luiza Hofmann, Oliver Markowetz, Florian McNeish, Iain A. Brenton, James D. |
| author_sort | Macintyre, Geoff |
| collection | PubMed |
| description | The genomic complexity of profound copy-number aberration has prevented effective molecular stratification of ovarian cancers. To decode this complexity, we derived copy-number signatures from shallow whole genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy-number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measuring signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes. |
| format | Online Article Text |
| id | pubmed-6130818 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-61308182019-02-13 Copy-number signatures and mutational processes in ovarian carcinoma Macintyre, Geoff Goranova, Teodora E. De Silva, Dilrini Ennis, Darren Piskorz, Anna M. Eldridge, Matthew Sie, Daoud Lewsley, Liz-Anne Hanif, Aishah Wilson, Cheryl Dowson, Suzanne Glasspool, Rosalind M. Lockley, Michelle Brockbank, Elly Montes, Ana Walther, Axel Sundar, Sudha Edmondson, Richard Hall, Geoff D. Clamp, Andrew Gourley, Charlie Hall, Marcia Fotopoulou, Christina Gabra, Hani Paul, James Supernat, Anna Millan, David Hoyle, Aoisha Bryson, Gareth Nourse, Craig Mincarelli, Laura Navarro Sanchez, Luis Ylstra, Bauke Jimenez-Linan, Mercedes Moore, Luiza Hofmann, Oliver Markowetz, Florian McNeish, Iain A. Brenton, James D. Nat Genet Article The genomic complexity of profound copy-number aberration has prevented effective molecular stratification of ovarian cancers. To decode this complexity, we derived copy-number signatures from shallow whole genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy-number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measuring signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes. 2018-08-13 2018-09 /pmc/articles/PMC6130818/ /pubmed/30104763 http://dx.doi.org/10.1038/s41588-018-0179-8 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Macintyre, Geoff Goranova, Teodora E. De Silva, Dilrini Ennis, Darren Piskorz, Anna M. Eldridge, Matthew Sie, Daoud Lewsley, Liz-Anne Hanif, Aishah Wilson, Cheryl Dowson, Suzanne Glasspool, Rosalind M. Lockley, Michelle Brockbank, Elly Montes, Ana Walther, Axel Sundar, Sudha Edmondson, Richard Hall, Geoff D. Clamp, Andrew Gourley, Charlie Hall, Marcia Fotopoulou, Christina Gabra, Hani Paul, James Supernat, Anna Millan, David Hoyle, Aoisha Bryson, Gareth Nourse, Craig Mincarelli, Laura Navarro Sanchez, Luis Ylstra, Bauke Jimenez-Linan, Mercedes Moore, Luiza Hofmann, Oliver Markowetz, Florian McNeish, Iain A. Brenton, James D. Copy-number signatures and mutational processes in ovarian carcinoma |
| title | Copy-number signatures and mutational processes in ovarian
carcinoma |
| title_full | Copy-number signatures and mutational processes in ovarian
carcinoma |
| title_fullStr | Copy-number signatures and mutational processes in ovarian
carcinoma |
| title_full_unstemmed | Copy-number signatures and mutational processes in ovarian
carcinoma |
| title_short | Copy-number signatures and mutational processes in ovarian
carcinoma |
| title_sort | copy-number signatures and mutational processes in ovarian
carcinoma |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130818/ https://www.ncbi.nlm.nih.gov/pubmed/30104763 http://dx.doi.org/10.1038/s41588-018-0179-8 |
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