HRD related signature 3 predicts clinical outcome in advanced tubo-ovarian high-grade serous carcinoma.

Autor: 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.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2024 Jan; Vol. 180, pp. 91-98. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1016/j.ygyno.2023.11.027
Abstrakt: 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.)
Databáze: MEDLINE
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