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

Philip Smith(University of Cambridge), Thomas Bradley(University of Cambridge), Lena Morrill Gavarró(University of Cambridge), Teodora Goranova(University of Cambridge), Darren Ennis(Ovarian Cancer Action), Hasan Mirza(Ovarian Cancer Action), Dilrini De Silva(University of Cambridge), Anna Piskorz(University of Cambridge), Carolin M. Sauer(University of Cambridge), Sarwah Al-Khalidi(University of Cambridge), Ionut-Gabriel Funingana(University of Cambridge), Marika Reinius(University of Cambridge), Gaia Giannone(Ovarian Cancer Action), Liz-Anne Lewsley(University of Glasgow), Jamie Stobo(University of Glasgow), John McQueen(University of Glasgow), Gareth Bryson(Queen Elizabeth University Hospital), Matthew Eldridge(University of Cambridge), The BriTROC Investigators(Beatson West of Scotland Cancer Centre), Rosalind Glasspool(Beatson West of Scotland Cancer Centre), Charlie Gourley(Queen's University Belfast), Richard D. Kennedy(Queen's University Belfast), Geoff Hall(University of Leeds), Richard J. Edmondson(University of Manchester), Andrew R. Clamp(The Christie NHS Foundation Trust), Sudha Sundar(At Bristol), A. Walter(At Bristol), Marcia Hall(Ovarian Cancer Action), Hani Gabra(Ovarian Cancer Action), C Fotopoulou(Barts Health NHS Trust), E. Brockbank(Guy's and St Thomas' NHS Foundation Trust), Ángela Guirao Montes(Queen Mary University of London), Michelle Lockley(Queen Mary University of London), Geoff Macintyre(University of Cambridge), Florian Markowetz(University of Cambridge), James D. Brenton(University of Cambridge), Iain A. McNeish(Ovarian Cancer Action)
Nature Communications
July 20, 2023
10.1038/s41467-023-39867-7
Cited by 56Open Access
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Abstract

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.

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