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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Article
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
Descripción
Sumario: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.

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