American Association for Cancer Research
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Supplementary Data from Multiomic Characterization of High-Grade Serous Ovarian Carcinoma Enables High-Resolution Patient Stratification

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posted on 2023-03-31, 23:43 authored by Robert L. Hollis, Alison M. Meynert, Caroline O. Michie, Tzyvia Rye, Michael Churchman, Amelia Hallas-Potts, Ian Croy, W. Glenn McCluggage, Alistair R.W. Williams, Clare Bartos, Yasushi Iida, Aikou Okamoto, Brian Dougherty, J. Carl Barrett, Ruth March, Athena Matakidou, Patricia Roxburgh, Colin A. Semple, D. Paul Harkin, Richard Kennedy, C. Simon Herrington, Charlie Gourley
Supplementary Data from Multiomic Characterization of High-Grade Serous Ovarian Carcinoma Enables High-Resolution Patient Stratification


MRC-funded fellowship

Target Ovarian Cancer

Tenovus Scotland

UK Medical Research Council



High-grade serous ovarian carcinoma (HGSOC) is the most common ovarian cancer type; most patients experience disease recurrence that accumulates chemoresistance, leading to treatment failure. Genomic and transcriptomic features have been associated with differential outcome and treatment response. However, the relationship between events at the gene sequence, copy number, and gene-expression levels remains poorly defined. We perform multiomic characterization of a large HGSOC cohort (n = 362) with detailed clinical annotation to interrogate the relationship between patient subgroups defined by specific molecular events. BRCA2-mutant (BRCA2m) and EMSY-overexpressing cases demonstrated prolonged survival [multivariable hazard ratios (HR) 0.40 and 0.51] and significantly higher first- and second-line chemotherapy response rate. CCNE1-gained (CCNE1g) cases demonstrated underrepresentation of FIGO stage IV cases, with shorter survival but no significant difference in treatment response. We demonstrate marked overlap between the TCGA- and Tothill-derived subtypes. IMR/C2 cases displayed higher BRCA1/2m frequency (25.5%, 32.5%) and significantly greater immune cell infiltration, whereas PRO/C5 cases had the highest CCNE1g rate (23.9%, 22.2%) and were uniformly low in immune cell infiltration. The survival benefit for cases with aberrations in homologous recombination repair (HRR) genes was apparent across all transcriptomic subtypes (HR range, 0.48–0.68). There was significant co-occurrence of RB loss and HRR gene aberrations; RB loss was further associated with favorable survival within HRR-aberrant cases (multivariable HR, 0.50). These data paint a high-resolution picture of the molecular landscape in HGSOC, better defining patients who may benefit most from specific molecular therapeutics and highlighting those for whom novel treatment strategies are needed to improve outcomes.

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