دورية أكاديمية
Multiomic Characterization of High-Grade Serous Ovarian Carcinoma Enables High-Resolution Patient Stratification.
| العنوان: | Multiomic Characterization of High-Grade Serous Ovarian Carcinoma Enables High-Resolution Patient Stratification. |
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| المؤلفون: | Hollis RL; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Meynert AM; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Michie CO; Edinburgh Cancer Centre, Western General Hospital, NHS Lothian, Edinburgh, UK., Rye T; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Churchman M; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Hallas-Potts A; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Croy I; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., McCluggage WG; Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK., Williams ARW; Division of Pathology, The Royal Infirmary of Edinburgh, Edinburgh, UK., Bartos C; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Iida Y; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.; The Jikei University School of Medicine, Tokyo, Japan., Okamoto A; The Jikei University School of Medicine, Tokyo, Japan., Dougherty B; Translational Medicine, Oncology R&D, AstraZeneca, Waltham, Massachusetts., Barrett JC; Translational Medicine, Oncology R&D, AstraZeneca, Waltham, Massachusetts., March R; Precision Medicine and Biosamples, Oncology R&D, AstraZeneca, Cambridge, UK., Matakidou A; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Roxburgh P; Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Belfast, UK.; Beatson West of Scotland Cancer Centre, Glasgow, UK., Semple CA; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Harkin DP; Almac Diagnostics, Craigavon, UK.; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK., Kennedy R; Almac Diagnostics, Craigavon, UK.; Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK., Herrington CS; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Gourley C; Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Aug 15; Vol. 28 (16), pp. 3546-3556. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Cystadenocarcinoma, Serous*/drug therapy , Cystadenocarcinoma, Serous*/genetics , Cystadenocarcinoma, Serous*/pathology , Ovarian Neoplasms*/drug therapy , Ovarian Neoplasms*/genetics , Ovarian Neoplasms*/pathology, Carcinoma, Ovarian Epithelial/genetics ; Female ; Genes, BRCA2 ; Humans ; Neoplasm Grading ; Neoplasm Recurrence, Local/genetics |
| مستخلص: | Purpose: 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. Experimental Design: 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. Results: 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). Conclusions: 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. (©2022 The Authors; Published by the American Association for Cancer Research.) |
| التعليقات: | Comment in: Transl Cancer Res. 2023 May 31;12(5):1368-1371. (PMID: 37304548) |
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| معلومات مُعتمدة: | I171113-1019 United Kingdom MRC_ Medical Research Council; MC_UU_00007/16 United Kingdom MRC_ Medical Research Council; United Kingdom CRUK_ Cancer Research UK |
| تواريخ الأحداث: | Date Created: 20220613 Date Completed: 20220816 Latest Revision: 20230612 |
| رمز التحديث: | 20230612 |
| مُعرف محوري في PubMed: | PMC9662902 |
| DOI: | 10.1158/1078-0432.CCR-22-0368 |
| PMID: | 35696721 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-22-0368 |