Journal article
Copy number signatures and mutational processes in ovarian carcinoma
G Macintyre, TE Goranova, D De Silva, D Ennis, AM Piskorz, M Eldridge, D Sie, LA Lewsley, A Hanif, C Wilson, S Dowson, RM Glasspool, M Lockley, E Brockbank, A Montes, A Walther, S Sundar, R Edmondson, GD Hall, A Clamp Show all
Nature Genetics | NATURE PORTFOLIO | Published : 2018
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 treatmen..
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Awarded by Cancer Research UK
Funding Acknowledgements
The BriTROC-1 study was funded by Ovarian Cancer Action (to I.A.M. and J.D.B., grant number 006). We acknowledge funding and support from Cancer Research UK (grant numbers A15973, A15601, A18072, A17197, A19274 and A19694), the Universities of Cambridge and Glasgow, National Institute for Health Research Cambridge and Imperial Biomedical Research Centres, National Cancer Research Network, the Experimental Cancer Medicine Centres at participating sites, the Beatson Endowment Fund and Hutchison Whampoa Limited. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank the Biorepository, Bioinformatics, Histopathology and Genomics Core Facilities of the Cancer Research UK Cambridge Institute and the Pathology Core at the Cancer Research UK Beatson Institute for technical support; members of the PCAWG Evolution and Heterogeneity Working Group for the consensus copy number analysis, the PCAWG Structural Variation Working Group for the consensus structural variants and the PCAWG Technical Working Group for annotating driver mutations in the 112 PCAWG-OV samples.