Article Text
Abstract
Introduction/Background 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.
Methodology 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). Alteration of the DNA damage response pathway was identified in 39.5% of high-grade serous carcinoma (HGSC), 25% of low-grade serous carcinoma (LGSC), and 24% of endometrioid carcinoma. BRCAness was identified in 38% of patients. TP53 mutation was the main oncogenic pathway in patients with HGSC (92.8%) and carcinosarcoma (87.5%). MAP kinase signaling was the main oncogenic pathway in LGSC (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 PFS, but not with 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 It is necessary to develop insight by identifying the overall oncogenic pattern and understanding the overall characteristics of the tumor. 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.
Disclosures The authors have no disclosure or potential conflicts of interest relevant to this article.