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

Smith, P. et al. (2023) The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma. Nature Communications, 14(1), 4387. (doi: 10.1038/s41467-023-39867-7) (PMID:37474499) (PMCID:PMC10359414)

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.

• Item Type: Articles
• Additional Information: 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.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcqueen, Mr John and Lewsley, Ms Liz-Anne and Mcneish, Professor Iain
• Authors: Smith, P., Bradley, T., Gavarró, L. M., Goranova, T., Ennis, D. P., Mirza, H. B., De Silva, D., Piskorz, A. M., Sauer, C., Al-Khalidi, S., Funingana, I.-G., Reinius, M. A. V., Giannone, G., Lewsley, L.-A., Stobo, J., Mcqueen, J., Bryson, G., Eldridge, M., Macintyre, G., Markowetz, F., Brenton, J. D., and McNeish, I. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © The Author(s) 2023
• First Published: First published in Nature Communications 14(1):4387
• Publisher Policy: Reproduced under a Creative Commons licence