Oncogenic pathway landscape of ovarian cancer and correlation with clinical prognosis.

Objective: We aimed to identify the main oncogenic pathway by histological type of ovarian cancer based on next-generation sequencing (NGS) test and to determine the correlation with clinical prognosis. Methods: We conducted a retrospective review of 420 patients with ovarian cancer who underwent NGS test at Asan Medical Center from June 1, 2017 to May 31, 2021. Identified mutations were categorized into seven oncogenic pathways that most frequently associated with ovarian cancer. Results: The average number of involved oncogenic pathways in each cancer patient was 1.76 (range, 0-6). TP53 mutation was the main oncogenic pathway in patients with high-grade serous ovarian carcinoma (HGSC) (92.8%) and carcinosarcoma (87.5%). MAP kinase signaling was the main oncogenic pathway in low-grade serous ovarian carcinoma (58.3%) and mucinous carcinoma (54.5%). The involvement of more diverse oncogenic pathways has been identified in patients with endometrioid carcinoma and clear cell carcinoma and PI3K-AKT-mTOR signaling and SWI/SNF family pathways were most common in both groups. FOXL2 mutation was confirmed in all three adult granulosa cell tumor patients. DNA damage response pathway involvement showed association with better progression-free survival (PFS), but not with overall survival (OS) in patients with HGSC. On the other hand, RTK signaling family pathway involvement showed an association with better OS despite no association with PFS in patients with HGSC. Conclusion: Endometrioid carcinoma and clear cell carcinoma show a diverse genetic profile, so standardized conventional chemotherapy is likely to be ineffective in many patients. Beyond this, clinical prognosis can be improved if targeted treatment tailored to the patient's genetic profile is implemented through NGS testing. [ABSTRACT FROM AUTHOR]