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The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma.

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Gavarró, Lena Morrill  ORCID logo
Goranova, Teodora 
Ennis, Darren P 


The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition of resistance by collecting tumour biopsies from a cohort of 276 women with relapsed ovarian high grade serous carcinoma in the BriTROC-1 study. Panel sequencing shows close concordance between diagnosis and relapse, with only four discordant cases. There is also very strong concordance in copy number between diagnosis and relapse, with no significant difference in purity, ploidy or focal somatic copy number alterations, even when stratified by platinum sensitivity or prior chemotherapy lines. Copy number signatures are strongly correlated with immune cell infiltration, whilst diagnosis samples from patients with primary platinum resistance have increased rates of CCNE1 and KRAS amplification and copy number signature 1 exposure. Our data show that the ovarian high grade serous carcinoma genome is remarkably stable between diagnosis and relapse and acquired chemotherapy resistance does not select for common copy number drivers.


Acknowledgements: This work was supported by Ovarian Cancer Action (grant number OCA_006 to IAMcN); the National Institute for Healthcare Research (NIHR) Imperial Biomedical Research Centre (grant number P77646 to IAMcN); the Wellcome Trust PhD programme in Mathematical Genomics and Medicine (grant number RG92770 to LMG); Cancer Research UK (grant numbers DRCQQR-Jun22\100005, A22905, A15601 and A26204 to JDB, FM and IAMcN); a European Society of Medical Oncology (ESMO) Translational Fellowship (to G.G.); the Beatson Cancer Charity and Hutchison Whampoa Limited. Infrastructure support was provided by CRUK/NIHR Experimental Cancer Medicine Centres at Imperial, Cambridge, Glasgow and other participating sites. We also thank the Biorepository, Bioinformatics, Histopathology, IT & Scientific Computing 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. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper.


Humans, Female, Ovarian Neoplasms, DNA Copy Number Variations, Neoplasm Recurrence, Local, Mutation, Cystadenocarcinoma, Serous

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Nat Commun

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Springer Science and Business Media LLC
Cancer Research UK (A22905)
Cancer Research UK (A15601)
Cancer Research UK (A19274)