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

Philip Smith, Thomas Bradley, Lena Morrill Gavarró, Teodora Goranova, Darren P. Ennis, Hasan B. Mirza, Dilrini Silva, Anna M. Piskorz, Carolin M. Sauer, Sarwah Al-Khalidi, Ionut-Gabriel Funingana, Marika A. V. Reinius, Gaia Giannone, Liz-Anne Lewsley, Jamie Stobo, John McQueen, Gareth Bryson, Matthew Eldridge, Geoff Macintyre, Florian Markowetz, James D. Brenton () and Iain A. McNeish ()
Additional contact information
Philip Smith: CRUK Cambridge Institute, University of Cambridge
Thomas Bradley: CRUK Cambridge Institute, University of Cambridge
Lena Morrill Gavarró: CRUK Cambridge Institute, University of Cambridge
Teodora Goranova: CRUK Cambridge Institute, University of Cambridge
Darren P. Ennis: Imperial College London
Hasan B. Mirza: Imperial College London
Dilrini Silva: CRUK Cambridge Institute, University of Cambridge
Anna M. Piskorz: CRUK Cambridge Institute, University of Cambridge
Carolin M. Sauer: CRUK Cambridge Institute, University of Cambridge
Sarwah Al-Khalidi: CRUK Cambridge Institute, University of Cambridge
Ionut-Gabriel Funingana: CRUK Cambridge Institute, University of Cambridge
Marika A. V. Reinius: CRUK Cambridge Institute, University of Cambridge
Gaia Giannone: Imperial College London
Liz-Anne Lewsley: University of Glasgow
Jamie Stobo: University of Glasgow
John McQueen: University of Glasgow
Gareth Bryson: Queen Elizabeth University Hospital
Matthew Eldridge: CRUK Cambridge Institute, University of Cambridge
Geoff Macintyre: CRUK Cambridge Institute, University of Cambridge
Florian Markowetz: CRUK Cambridge Institute, University of Cambridge
James D. Brenton: CRUK Cambridge Institute, University of Cambridge
Iain A. McNeish: Imperial College London

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39867-7

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