The Genomic Landscape of Early-Stage Ovarian High-Grade Serous Carcinoma.

Autor:	Cheng Z; Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom., Mirza H; Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom., Ennis DP; Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom., Smith P; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Morrill Gavarró L; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Sokota C; Department of Cellular Pathology, Imperial College Healthcare NHS Trust, London, United Kingdom., Giannone G; Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom.; Department of Oncology, University of Turin, Turin, Italy., Goranova T; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Bradley T; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Piskorz A; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Lockley M; Centre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom., Kaur B; Department of Cellular Pathology, Imperial College Healthcare NHS Trust, London, United Kingdom., Singh N; Department of Pathology, Barts Healthcare NHS Trust, London, United Kingdom., Tookman LA; Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom., Krell J; Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom., McDermott J; Department of Pathology, University College London Hospital NHS Trust, London, United Kingdom., Macintyre G; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Markowetz F; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., Brenton JD; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom., McNeish IA; Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Jul 01; Vol. 28 (13), pp. 2911-2922.
DOI:	10.1158/1078-0432.CCR-21-1643
Abstrakt:	Purpose: Ovarian high-grade serous carcinoma (HGSC) is usually diagnosed at late stage. We investigated whether late-stage HGSC has unique genomic characteristics consistent with acquisition of evolutionary advantage compared with early-stage tumors. Experimental Design: We performed targeted next-generation sequencing and shallow whole-genome sequencing (sWGS) on pretreatment samples from 43 patients with FIGO stage I-IIA HGSC to investigate somatic mutations and copy-number (CN) alterations (SCNA). We compared results to pretreatment samples from 52 patients with stage IIIC/IV HGSC from the BriTROC-1 study. Results: Age of diagnosis did not differ between early-stage and late-stage patients (median 61.3 years vs. 62.3 years, respectively). TP53 mutations were near-universal in both cohorts (89% early-stage, 100% late-stage), and there were no significant differences in the rates of other somatic mutations, including BRCA1 and BRCA2. We also did not observe cohort-specific focal SCNA that could explain biological behavior. However, ploidy was higher in late-stage (median, 3.0) than early-stage (median, 1.9) samples. CN signature exposures were significantly different between cohorts, with greater relative signature 3 exposure in early-stage and greater signature 4 in late-stage. Unsupervised clustering based on CN signatures identified three clusters that were prognostic. Conclusions: Early-stage and late-stage HGSCs have highly similar patterns of mutation and focal SCNA. However, CN signature analysis showed that late-stage disease has distinct signature exposures consistent with whole-genome duplication. Further analyses will be required to ascertain whether these differences reflect genuine biological differences between early-stage and late-stage or simply time-related markers of evolutionary fitness. See related commentary by Yang et al., p. 2730. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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