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 testing at Asan Medical Center from June 1, 2017, to May 31, 2021. Identified mutations were categorized into seven oncogenic pathways that are most frequently associated with ovarian cancer.

Results: The average number of oncogenic pathways involved in each cancer patient was 1.76 (range, 0-6). TP53 mutation was the primary oncogenic pathway in patients with high-grade serous carcinoma (HGSC) (92.8%) and carcinosarcoma (87.5%). MAP kinase signaling was the primary oncogenic pathway in low-grade serous 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 the most common in both groups. The involvement of the DNA damage response pathway showed an association with better progression free survival (PFS), but not with overall survival (OS) in patients with HGSC. On the other hand, the involvement of the RTK signaling family pathway showed an association with better OS despite no association with PFS in patients with HGSC.

Conclusion: The clinical prognosis may be improved by implementing targeted treatment tailored to the patient's genetic profile through NGS. Additional research is needed to determine whether the involvement of the RTK signaling family pathway is indeed associated with better OS and to identify the underlying reasons for this association.