Tumor Genotyping and Homologous Recombination Repair Gene Variants in Patients With Epithelial Ovarian Cancer: Is Pathogenic Enough?
Year: 2021
Type: article
Study design: Observational Study
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].
Source: Frontiers in Oncology
Authors: Elena Fountzilas, Vassiliki Kotoula, Georgia-Angeliki Koliou, Michalis Liontos, Kyriaki Papadopoulou, Eleni Giannoulatou, Alexios Papanikolaou, Ioannis Tikas, Sofia Chrisafi, Davide Mauri, Kyriakos Chatzopoulos, Florentia Fostira, Dimitrios Pectasides, Georgios Oikonomopoulos, Dimitra Aivazi, Angeliki Andrikopoulou, Anastasios Visvikis, Gerasimos Aravantinos, Flora Zagouri, George Fountzilas
Institutions: Euromedica, Aristotle University of Thessaloniki, Hellenic Cooperative Oncology Group, National and Kapodistrian University of Athens, Alexandra Hospital, Victor Chang Cardiac Research Institute, UNSW Sydney, Papageorgiou General Hospital, University of Ioannina, National Centre of Scientific Research "Demokritos", Hippocration General Hospital, Metropolitan Hospital, Limassol General Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
OpenAlex ID: W3170225522