AUTHOR=Fountzilas Elena , Kotoula Vassiliki , Koliou Georgia-Angeliki , Liontos Michalis , Papadopoulou Kyriaki , Giannoulatou Eleni , Papanikolaou Alexios , Tikas Ioannis , Chrisafi Sofia , Mauri Davide , Chatzopoulos Kyriakos , Fostira Florentia , Pectasides Dimitrios , Oikonomopoulos Georgios , Aivazi Dimitra , Andrikopoulou Angeliki , Visvikis Anastasios , Aravantinos Gerasimos , Zagouri Flora , Fountzilas George 

TITLE=Tumor Genotyping and Homologous Recombination Repair Gene Variants in Patients With Epithelial Ovarian Cancer: Is Pathogenic Enough?

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.683057

DOI=10.3389/fonc.2021.683057

ISSN=2234-943X

ABSTRACT=<p>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 &gt;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/<italic>TP53</italic> 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.</p><sec><title>Clinical Trial Registration</title><p>[<uri xlink:href="https://www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</uri>], identifier [NCT04716374].</p></sec>