Genomic and clinical insights into ovarian cancer: subtype-specific alterations and predictors of metastasis and relapse

Ovarian cancer exhibits marked molecular heterogeneity and variable clinical outcomes. Understanding genomic alterations associated with metastasis and relapses may guide personalized management, particularly in high-grade serous carcinoma (HGSC). We performed targeted sequencing of 1021 cancer-related genes in tumor-normal pairs from 99 treatment-naïve ovarian cancer patients. Associations between copy number variations (CNVs), metastatic patterns, tumor mutation burden (TMB), and relapses were assessed. Analyses of relapse predictors were restricted to HGSC patients. Statistical significance was determined with Bonferroni correction for multiple comparisons. TP53 mutations were frequent in HGSC (96.6%), whereas PIK3CA, ARID1A, and ATRX mutations were enriched in non-HGSC tumors. FLT3, CDH23, and EPAS1 mutations were associated with metastasis. TMB-high tumors (≥ 9 mutations/Mb) showed distinct profiles, including SMARCA4 and FUBP1 mutations and CNV gains in CEBPA. Among HGSC patients, TBX3 mutations were exclusively observed in those relapsing within six months (p = 0.028), while ARID1B, MAP2K1, and FLT4 were enriched in relapse groups. After neoadjuvant chemotherapy and FIGO stage IV were also associated with relapses. This study reveals subtype-specific and metastasis-related genomic alterations in ovarian cancer and identifies potential relapse-associated mutations in HGSC. While exploring, these findings support further investigation into individualized risk stratification and biomarker-driven therapeutic strategies.