Detection of Circulating Tumor Dna in Ovarian Clear Cell Carcinoma

Epithelial ovarian carcinoma is often presented in an advanced stage at diagnosis. It consisted of a plethora of neoplasms, with the most common histological subtypes of high-grade serous and clear cell carcinoma. Ovarian clear cell carcinoma is a unique form of ovarian cancer that prevails in Taiwan with the prevalence much higher than the western countries. Our previous studies showed that early stage ovarian clear cell carcinoma is more prevalent than high-grade serous carcinoma (HGSC) but in recurrence settings, even in stage I disease, the prognosis is worse than the HGSC counterpart. Therefore, the distinct characteristics of ovarian clear cell carcinoma underscores the importance of early detection of recurrence in addition to minimal residual disease. Furthermore, neither cancer antigen-125 nor human epididymis 4 is a good tumor marker for the diagnosis and monitoring recurrence of ovarian clear cell carcinoma.Currently, the only cell-free DNA-based tests approved by the Food and Drug Administration are The Cobas EGFR Mutation Test which detects EGFR mutations in patients with lung cancer and EpiColon which detects the methylation status of the SEPT9 promoter for patients receiving screening for colorectal cancer. Analyzing circulating tumor DNA (ctDNA) using next generation sequencing (NGS) is one of the common approaches to real-time detect tumor fragments in the peripheral blood. Nevertheless, the amount of ctDNAs in the peripheral blood is highly variable in different cancer types, tumor anatomic location, mitotic rates, and vascularization. The abundance of ctDNA is measured with mutant allele frequency (MAF). A number of studies on ctDNA in ovarian cancer focusing on HGSC have been reported to test for the clinical utility in diagnosis, prognosis, and treatment monitoring utilizing targeted NGS. The evaluation of ctDNA on ovarian clear cell carcinoma is, however, scarce. In this two-year project, we aim to (1) Identify the sensitivity of sequencing ctDNA with ACTmonitor®+ 50 panel for ovarian clear cell carcinoma; (2) Determine the correlation between tumor volume (stage) and MAF; (3) Determine whether ctDNA predicts recurrence better than other biomarkers/imaging exams; (4) Determine whether a decrease in MAF predicts treatment response in real time; (5) Identify mutations not detected in formalin-fixed paraffin-embedded samples are identified in ctDNA; (6) Provide information of targeted therapies for patients with ovarian clear cell carcinoma. The findings of the sequencing data in this study will characterize the molecular characteristics of this cohort of patients with ovarian clear cell carcinoma. Patients can be monitored with ctDNA and protein biomarkers in different clinical settings. Patients who are refractory to standard treatments might have real-time alternative therapeutic strategies based on the molecular profiling. Clinical implications of ctDNA will ultimately be established.

Project ID:PC10907-1129
External Project ID:MOST109-2314-B182A-167