Ovarian cancer is the deadliest gynecologic malignancy largely due to late diagnosis. The present study aims to provide a comprehensive assessment of clinically relevant and potentially actionable germline and somatic pathways in ovarian cancer through parallel analysis of inherited susceptibility and tumor-specific genomic alterations, within the constraints of targeted NGS panel design.

We analyzed 33 Bulgarian women with histologically confirmed ovarian cancer. Next‑generation sequencing (NGS) was performed on germline DNA from peripheral blood and tumor DNA from FFPE tissue. Variants were described per HGVS, classified by ACMG/AMP (germline) and AMP/ASCO/CAP (somatic), and reviewed in ClinVar/COSMIC. Descriptive statistics were generated in Python.

All pathogenic and likely pathogenic germline and somatic variants are summarized in comprehensive tables. Somatic pathogenic TP53 variants were identified in 27/33 patients (81.8%). Germline pathogenic/likely pathogenic variants were detected in 9/33 (27.3%), most commonly in BRCA1 (3/33; 9.1%), with single cases in ATM, RAD51D, NBN, FANCL and WRN. One patient fulfilled criteria for multi‑locus inherited neoplasia alleles syndrome (MINAS). High‑grade serous ovarian histological subtype predominated (75.8%).

Dual-sample NGS enables an integrated evaluation of hereditary risk and tumor-associated actionable alterations in ovarian cancer. While comprehensive interrogation of all therapeutic pathways is limited by panel scope, this approach supports clinically meaningful stratification and highlights areas requiring expanded molecular testing.