Global characterization of extrachromosomal circular DNAs in advanced high grade serous ovarian cancer

Abstract

High grade serous ovarian cancer (HGSOC) is the most aggressive subtype of ovarian cancer and HGSOC patients often appear with metastasis, leading to the poor prognosis. Up to date, the extrachromosomal circular DNAs (eccDNAs) have been shown to be involved in cancer genome remodeling but the roles of eccDNAs in metastatic HGSOC are still not clear. Here we explored eccDNA profiles in HGSOC by Circle-Sequencing analysis using four pairs of primary and metastatic tissues of HGSOC patients. Within the differentially expressed eccDNAs screened out by our analysis, eight candidates were validated by outward PCR and qRT-PCR analysis. Among them, DNMT1circle10302690-10302961 was further confirmed by FISH assay and BaseScope assay, as the most significantly down-regulated eccDNA in metastatic tumors of HGSOC. Lower expression of DNMT1circle10302690-10302961 in both primary and metastatic tumors was associated with worse prognosis of HGSOC. Taken together, our finding firstly demonstrated the eccDNAs landscape of primary and metastatic tissues of HGSOC. The eccDNA DNMT1circle10302690-10302961 can be considered as a potential biomarker or a therapeutically clinical target of HGSOC metastasis and prognosis.