Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer
IntroductionOvarian cancer (OC) is one of the leading causes of cancer-related death in women worldwide. Treatment with PARP-inhibitors has significantly improved survival in patients with high-grade serous cancer (HGSC) bearing BRCA1/2 mutations (~22% of the cases), and/or homologous recombination...
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Frontiers Media S.A.
2025-08-01
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| author | Elena Conca Daniele Lorenzini Daniele Lorenzini Emanuela Minna Luca Agnelli Matteo Duca Marco Gentili Beatrice Bodini Maggie Polignano Mara Mantiero Silvia Damian Andrea Devecchi Gianpaolo Dagrada Rita Carminati Alice Ardore Francesca Barbetta Nathalia Brito Da Chuna Andrea Guerrizio Adele Busico Iolanda Capone Alberta Piccolo Elena Tamborini Federica Perrone Massimo Milione Biagio Paolini Andrea Vingiani Andrea Vingiani Francesco Raspagliesi Francesco Raspagliesi Filippo De Braud Filippo De Braud Giancarlo Pruneri Giancarlo Pruneri |
| author_facet | Elena Conca Daniele Lorenzini Daniele Lorenzini Emanuela Minna Luca Agnelli Matteo Duca Marco Gentili Beatrice Bodini Maggie Polignano Mara Mantiero Silvia Damian Andrea Devecchi Gianpaolo Dagrada Rita Carminati Alice Ardore Francesca Barbetta Nathalia Brito Da Chuna Andrea Guerrizio Adele Busico Iolanda Capone Alberta Piccolo Elena Tamborini Federica Perrone Massimo Milione Biagio Paolini Andrea Vingiani Andrea Vingiani Francesco Raspagliesi Francesco Raspagliesi Filippo De Braud Filippo De Braud Giancarlo Pruneri Giancarlo Pruneri |
| author_sort | Elena Conca |
| collection | DOAJ |
| description | IntroductionOvarian cancer (OC) is one of the leading causes of cancer-related death in women worldwide. Treatment with PARP-inhibitors has significantly improved survival in patients with high-grade serous cancer (HGSC) bearing BRCA1/2 mutations (~22% of the cases), and/or homologous recombination deficiency (HRD, ~50%). Unfortunately, limited therapeutic alternatives are available for BRCA1/2 wild type/HR proficient HGSC patients, who usually exhibit resistance to standard treatments and poor prognosis.MethodsHerein, we present the results of a comprehensive genomic profiling (CGP) analysis using the Oncomine Comprehensive Assay® (OCA) Plus in a consecutive retrospective cohort of 102 HGSC patients characterized in our institution.ResultsGenomic instability, measured by Genomic Instability Metric (GIM) >16, was found in 40% of the cases and was significantly associated with BRCA1/2 mutations (p=0.009), with a better prognosis in terms of recurrence-free survival (p=0.01). CCNE1 amplification was observed in 29% of cases and was negatively correlated with BRCA1/2 mutations (p=0.001), without any association with GIM, supporting CCNE1 as a strong and independent driver of tumorigenesis. Additionally, CCNE1 amplification was validated with fluorescent in situ hybridization (FISH), supporting the analytical robustness of NGS data (rho=0.93), and investigated by immunohistochemistry (IHC), revealing that CCNE1 protein overexpression was observed in the absence of gene amplification in 45% of cases.DiscussionOur real-world study supports the clinical utility of the GIM metric and the analytical validity of CCNE1 amplification, a new promising biomarker for personalizing treatment in HR proficient HGSC patients. The discordance between CCNE1 amplification and protein expression raises intriguing questions about the mechanisms of CCNE1-driven tumorigenesis and warrants further investigation. |
| format | Article |
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| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-08-01 |
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| series | Frontiers in Oncology |
| spelling | doaj-art-25eb9be25ddd46f6b0760ce1738c1e0e2025-08-20T03:59:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16334101633410Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancerElena Conca0Daniele Lorenzini1Daniele Lorenzini2Emanuela Minna3Luca Agnelli4Matteo Duca5Marco Gentili6Beatrice Bodini7Maggie Polignano8Mara Mantiero9Silvia Damian10Andrea Devecchi11Gianpaolo Dagrada12Rita Carminati13Alice Ardore14Francesca Barbetta15Nathalia Brito Da Chuna16Andrea Guerrizio17Adele Busico18Iolanda Capone19Alberta Piccolo20Elena Tamborini21Federica Perrone22Massimo Milione23Biagio Paolini24Andrea Vingiani25Andrea Vingiani26Francesco Raspagliesi27Francesco Raspagliesi28Filippo De Braud29Filippo De Braud30Giancarlo Pruneri31Giancarlo Pruneri32Department of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Pathology and Laboratory Medicine, Pathology Unit 1, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Pathology and Laboratory Medicine, Pathology Unit 1, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyGynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyGynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Pathology and Laboratory Medicine, Pathology Unit 1, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Pathology and Laboratory Medicine, Pathology Unit 1, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milano, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milano, ItalyGynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milano, ItalyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyDepartment of Oncology and Hemato-Oncology, University of Milan, Milano, ItalyIntroductionOvarian cancer (OC) is one of the leading causes of cancer-related death in women worldwide. Treatment with PARP-inhibitors has significantly improved survival in patients with high-grade serous cancer (HGSC) bearing BRCA1/2 mutations (~22% of the cases), and/or homologous recombination deficiency (HRD, ~50%). Unfortunately, limited therapeutic alternatives are available for BRCA1/2 wild type/HR proficient HGSC patients, who usually exhibit resistance to standard treatments and poor prognosis.MethodsHerein, we present the results of a comprehensive genomic profiling (CGP) analysis using the Oncomine Comprehensive Assay® (OCA) Plus in a consecutive retrospective cohort of 102 HGSC patients characterized in our institution.ResultsGenomic instability, measured by Genomic Instability Metric (GIM) >16, was found in 40% of the cases and was significantly associated with BRCA1/2 mutations (p=0.009), with a better prognosis in terms of recurrence-free survival (p=0.01). CCNE1 amplification was observed in 29% of cases and was negatively correlated with BRCA1/2 mutations (p=0.001), without any association with GIM, supporting CCNE1 as a strong and independent driver of tumorigenesis. Additionally, CCNE1 amplification was validated with fluorescent in situ hybridization (FISH), supporting the analytical robustness of NGS data (rho=0.93), and investigated by immunohistochemistry (IHC), revealing that CCNE1 protein overexpression was observed in the absence of gene amplification in 45% of cases.DiscussionOur real-world study supports the clinical utility of the GIM metric and the analytical validity of CCNE1 amplification, a new promising biomarker for personalizing treatment in HR proficient HGSC patients. The discordance between CCNE1 amplification and protein expression raises intriguing questions about the mechanisms of CCNE1-driven tumorigenesis and warrants further investigation.https://www.frontiersin.org/articles/10.3389/fonc.2025.1633410/fullhigh-grade serous ovarian cancer (HGSC)comprehensive genomic profiling (CGP)homologous recombination deficiency (HRD) scoreCCNE1 amplificationprecision oncology cancer |
| spellingShingle | Elena Conca Daniele Lorenzini Daniele Lorenzini Emanuela Minna Luca Agnelli Matteo Duca Marco Gentili Beatrice Bodini Maggie Polignano Mara Mantiero Silvia Damian Andrea Devecchi Gianpaolo Dagrada Rita Carminati Alice Ardore Francesca Barbetta Nathalia Brito Da Chuna Andrea Guerrizio Adele Busico Iolanda Capone Alberta Piccolo Elena Tamborini Federica Perrone Massimo Milione Biagio Paolini Andrea Vingiani Andrea Vingiani Francesco Raspagliesi Francesco Raspagliesi Filippo De Braud Filippo De Braud Giancarlo Pruneri Giancarlo Pruneri Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer Frontiers in Oncology high-grade serous ovarian cancer (HGSC) comprehensive genomic profiling (CGP) homologous recombination deficiency (HRD) score CCNE1 amplification precision oncology cancer |
| title | Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer |
| title_full | Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer |
| title_fullStr | Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer |
| title_full_unstemmed | Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer |
| title_short | Genomic instability and CCNE1 amplification as emerging biomarkers for stratifying high-grade serous ovarian cancer |
| title_sort | genomic instability and ccne1 amplification as emerging biomarkers for stratifying high grade serous ovarian cancer |
| topic | high-grade serous ovarian cancer (HGSC) comprehensive genomic profiling (CGP) homologous recombination deficiency (HRD) score CCNE1 amplification precision oncology cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1633410/full |
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