Copy number signatures and mutational processes in ovarian carcinoma

Geoff Macintyre, Teodora E. Goranova, Dilrini De Silva, Darren Ennis, Anna M. Piskorz, Matthew Eldridge, Daoud Sie, Liz Anne Lewsley, Aishah Hanif, Cheryl Wilson, Suzanne Dowson, Rosalind M. Glasspool, Michelle Lockley, Elly Brockbank, Ana Montes, Axel Walther, Sudha Sundar, Richard Edmondson, Geoff D. Hall, Andrew ClampCharlie Gourley, Marcia Hall, Christina Fotopoulou, Hani Gabra, James Paul, Anna Supernat, David Millan, Aoisha Hoyle, Gareth Bryson, Craig Nourse, Laura Mincarelli, Luis Navarro Sanchez, Bauke Ylstra, Mercedes Jimenez-Linan, Luiza Moore, Oliver Hofmann, Florian Markowetz*, Iain A. McNeish, James D. Brenton

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, 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. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.

Original languageEnglish
Pages (from-to)1262-1270
Number of pages9
JournalNature Genetics
Volume50
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

Cite this

Macintyre, G., Goranova, T. E., De Silva, D., Ennis, D., Piskorz, A. M., Eldridge, M., ... Brenton, J. D. (2018). Copy number signatures and mutational processes in ovarian carcinoma. Nature Genetics, 50(9), 1262-1270. https://doi.org/10.1038/s41588-018-0179-8