Exploring the somatic mutational landscape of ovarian cancer in Estonia.

This retrospective study provides Estonia's first nationwide overview of pathogenic and likely pathogenic variants in ovarian cancer (OC) using routine tumor molecular profiling. The aim was to characterize the mutational landscape, identify clinically actionable alterations, and evaluate the integration of germline testing. Patient/material and methods: A total of 339 OC tumor samples underwent next‑generation sequencing-based profiling. Clinical characteristics, histological subtype, and prior germline testing were recorded. Variants were classified according to clinical‑actionability levels, and homologous recombination deficiency (HRD) was assessed in high‑grade serous OC cases. The mean age at diagnosis was 62.4 ± 12.5 years, and high‑grade serous OC accounted for 82.0% of cases. Clinically actionable alterations (OncoKB Level 1&2) were detected in 37.5% of patients, most frequently involving BRCA1, BRCA2, KRAS, and BRAF. Additional therapeutic targets were identified across diverse biomarkers. HRD was present in 53.2% of tested high‑grade serous tumors. Germline testing had been performed in 41.9% of patients, revealing pathogenic or likely pathogenic variants in 22.5%, predominantly in BRCA1 and BRCA2. This study outlines the mutational spectrum of OC in Estonia and demonstrates a substantial prevalence of actionable alterations and HRD. The findings highlight the value of comprehensive tumor profiling to support precision‑medicine approaches and improve individualized patient management in Estonia.