TY - JOUR T1 - Copy-number signatures and mutational processes in ovarian carcinoma JF - bioRxiv DO - 10.1101/174201 SP - 174201 AU - Geoff Macintyre AU - Teodora E. Goranova AU - Dilrini De Silva AU - Darren Ennis AU - Anna M. Piskorz AU - Matthew Eldridge AU - Daoud Sie AU - Liz-Anne Lewsley AU - Aishah Hanif AU - Cheryl Wilson AU - Suzanne Dowson AU - Rosalind M. Glasspool AU - Michelle Lockley AU - Elly Brockbank AU - Ana Montes AU - Axel Walther AU - Sudha Sundar AU - Richard Edmondson AU - Geoff D. Hall AU - Andrew Clamp AU - Charlie Gourley AU - Marcia Hall AU - Christina Fotopoulou AU - Hani Gabra AU - James Paul AU - Anna Supernat AU - David Millan AU - Aoisha Hoyle AU - Gareth Bryson AU - Craig Nourse AU - Laura Mincarelli AU - Luis Navarro Sanchez AU - Bauke Ylstra AU - Mercedes Jimenez-Linan AU - Luiza Moore AU - Oliver Hofmann AU - Florian Markowetz AU - Iain A. McNeish AU - James D. Brenton Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/09/04/174201.abstract N2 - Genomic complexity from profound copy-number aberration has prevented effective molecular stratification of ovarian and other cancers. Here we present a method for copy-number signature identification that decodes this complexity. We derived eight signatures using 117 shallow whole-genome sequenced high-grade serous ovarian cancer cases, which were validated on a further 497 cases. Mutational processes underlying the copy-number signatures were identified, including breakage-fusion-bridge cycles, homologous recombination deficiency and whole-genome duplication. We show that most tumours are heterogeneous and harbour multiple signature exposures. We also demonstrate that copy number signatures predict overall survival and changes in signature exposure observed in response to chemotherapy suggest potential treatment strategies. ER -