Fountzilas, Elena and Kotoula, Vassiliki and Koliou, Georgia-Angeliki and Liontos, Michalis and Papadopoulou, Kyriaki and Giannoulatou, Eleni and Papanikolaou, Alexios and Tikas, Ioannis and Chrisafi, Sofia and Mauri, Davide and Chatzopoulos, Kyriakos and Fostira, Florentia and Pectasides, Dimitrios and Oikonomopoulos, Georgios and Aivazi, Dimitra and Andrikopoulou, Angeliki and Visvikis, Anastasios and Aravantinos, Gerasimos and Zagouri, Flora and Fountzilas, George (2021) Tumor Genotyping and Homologous Recombination Repair Gene Variants in Patients With Epithelial Ovarian Cancer: Is Pathogenic Enough? Frontiers in Oncology, 11. ISSN 2234-943X
Full text not available from this repository.Abstract
Our hypothesis was that the predictive accuracy of pathogenic variants in genes participating in the homologous recombination repair (HRR) system in patients with epithelial ovarian cancer (EOC) could be improved by considering additional next-generation sequencing (NGS) metrics. NGS genotyping was performed in tumor tissue, retrospectively and prospectively collected from patients with EOC, diagnosed from 8/1998 to 10/2016. Variants were considered clonal when variant allele frequencies corresponded to >25%. The primary endpoint was overall survival (OS). This study included 501 patients with EOC, predominantly with high-grade serous (75.2%) and advanced stage tumors (81.7%); median age was 58 years (22-84). Pathogenic and clonal pathogenic variants in HRR and/or TP53 genes were identified in 72.8% and 66.5% tumors, respectively. With a median follow-up of 123.9 months, the presence of either pathogenic or clonal pathogenic HRR-only variants was associated with longer OS compared to HRR/TP53 co-mutation (HR=0.54; 95% CI, 0.34-0.87, Wald's p=0.012 and HR=0.45; 95% CI, 0.27-0.78, Wald's p=0.004, respectively). However, only the presence of clonal HRR-only variants was independently associated with improved OS (HR=0.55; 95% CI, 0.32-0.94, p=0.030). Variant clonality and co-occuring TP53 variants affect the predictive value of HRR pathogenic variants for platinum agents in patients with EOC. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04716374].
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 31 Jul 2021 04:26 |
| Last Modified: | 31 Jul 2021 04:26 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1081 |
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