Germline Mutational Spectrum in Ovarian Cancer: A Descriptive Study from a Tertiary Cancer Center

Ovarian cancer (OC) is a leading cause of gynecologic cancer mortality worldwide, with notable regional and ethnic variation in incidence, histology, and genetic drivers. Limited screening options often delay diagnosis, and many cases occur without a family history, emphasizing the need for broader genetic evaluation. While BRCA1/2 mutations account for most hereditary OC, additional susceptibility genes are increasingly recognized. Regional genetic data, however, remain scarce, particularly from India. This retrospective study investigates the clinical and molecular characteristics of OC patients treated at a single tertiary center in Western India, examining mutation patterns, hotspot regions, and variant types. By comparing these findings with documented international cohorts, the study highlights the necessity of dynamic variant reclassification in local clinical practice to improve personalized management and genetic counseling. This study characterizes local OC clinico-demographic and genetic findings, including mutational gene hotspots, compares BRCA and non-BRCA variants and contextualizes these findings within the existing global literature to improve local variant interpretation and patient care. This retrospective study analyzed data from 82 patients with OC tested between 2022 and 2025 at a tertiary center in Western India. Frequencies and percentages were used as statistical descriptors. To contextualize our findings, a literature-based comparative analysis was conducted against published data from Asian, Caucasian, Chinese, and American cohorts. A case of a variant of uncertain significance with damaging effect (VUSD) reclassification was also examined. Maximum incidence occurred in the 50 to 60 year age group. A notable 50% of patients with clinically relevant mutations reported no family history of cancer. Serous carcinoma emerged as the principal histological type. Genetic profiling revealed BRCA1/BRCA2 exons 10/11 as mutational hotspots. In the BRCA cohort, the majority of variants were classified as pathogenic or likely pathogenic (LP), whereas the non-BRCA cohort was characterized by a predominance of variants of uncertain significance (VUS). One VUSD case was reclassified as pathogenic, contributing to the precision-targetable mutation burden for the patient. While the serous histology and BRCA hotspots in our cohort align with global trends, the high mutation rates observed emphasize the need for robust institutional data. The reclassification of a VUSD case highlights the dynamic nature of variant interpretation and supports the clinical utility of routine re-evaluation to optimize genetic counseling and personalized care.