دورية أكاديمية
HRD related signature 3 predicts clinical outcome in advanced tubo-ovarian high-grade serous carcinoma.
| العنوان: | HRD related signature 3 predicts clinical outcome in advanced tubo-ovarian high-grade serous carcinoma. |
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| المؤلفون: | Koskela H; Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland., Li Y; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Joutsiniemi T; Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland., Muranen T; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Isoviita VM; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Huhtinen K; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Institute of Biomedicine and FICAN West Cancer Centre, University of Turku and Turku University Hospital, Turku, Finland., Micoli G; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Lavikka K; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Marchi G; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Hietanen S; Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland., Virtanen A; Department of Pathology, University of Helsinki and HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Hautaniemi S; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Oikkonen J; Research Program in Systems Oncology, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Hynninen J; Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, Turku, Finland. Electronic address: mijohy@utu.fi. |
| المصدر: | Gynecologic oncology [Gynecol Oncol] 2024 Jan; Vol. 180, pp. 91-98. Date of Electronic Publication: 2023 Dec 06. |
| نوع المنشور: | Clinical Trial; Journal Article; Observational Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0365304 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-6859 (Electronic) Linking ISSN: 00908258 NLM ISO Abbreviation: Gynecol Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, Academic Press. |
| مواضيع طبية MeSH: | Cystadenocarcinoma, Serous*/pathology , Ovarian Neoplasms*/pathology, Female ; Humans ; Cicatrix/pathology ; Prognosis ; Progression-Free Survival |
| مستخلص: | Objectives: We evaluated usability of single base substitution signature 3 (Sig3) as a biomarker for homologous recombination deficiency (HRD) in tubo-ovarian high-grade serous carcinoma (HGSC). Materials and Methods: This prospective observational trial includes 165 patients with advanced HGSC. Fresh tissue samples (n = 456) from multiple intra-abdominal areas at diagnosis and after neoadjuvant chemotherapy (NACT) were collected for whole-genome sequencing. Sig3 was assessed by fitting samples independently with COSMIC v3.2 reference signatures. An HR scar assay was applied for comparison. Progression-free survival (PFS) and overall survival (OS) were studied using Kaplan-Meier and Cox regression analysis. Results: Sig3 has a bimodal distribution, eliminating the need for an arbitrary cutoff typical in HR scar tests. Sig3 could be assessed from samples with low (10%) cancer cell proportion and was consistent between multiple samples and stable during NACT. At diagnosis, 74 (45%) patients were HRD (Sig3+), while 91 (55%) were HR proficient (HRP, Sig3-). Sig3+ patients had longer PFS and OS than Sig3- patients (22 vs. 13 months and 51 vs. 34 months respectively, both p < 0.001). Sig3 successfully distinguished the poor prognostic HRP group among BRCAwt patients (PFS 19 months for Sig3+ and 13 months for Sig3- patients, p < 0.001). However, Sig3 at diagnosis did not predict chemoresponse anymore in the first relapse. The patient-level concordance between Sig3 and HR scar assay was 87%, and patients with HRD according to both tests had the longest median PFS. Conclusions: Sig3 is a prognostic marker in advanced HGSC and useful tool in patient stratification for HRD. Competing Interests: Declaration of Competing Interest We have no conflicts of interest to disclose. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Genetic testing; High-grade serous ovarian cancer (HGSC); Homologous-recombination-deficiency (HRD); Platinum; Whole-genome-sequencing (WGS) |
| تواريخ الأحداث: | Date Created: 20231207 Date Completed: 20240219 Latest Revision: 20240228 |
| رمز التحديث: | 20240228 |
| DOI: | 10.1016/j.ygyno.2023.11.027 |
| PMID: | 38061276 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1095-6859 |
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| DOI: | 10.1016/j.ygyno.2023.11.027 |