Transcriptomic profiling and functional characterization of fusion genes in recurrent ovarian cancer
Technical Report,15 Aug 2016,14 Aug 2019
University of Pittsburgh Pittsburgh United States
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High-grade serous ovarian cancer HGSOC is known for its lack of early detection, limited therapies, and high rate of recurrence. Recent advances in transcriptomic sequencing have identified drug-targetable, pathogenic fusion genes in solid cancers. We hypothesize that fusion genes are commonly acquired or enriched in relapsed HGSOC and contribute to the enhanced malignancy observed in recurrent disease. We assembled a cohort of 18 patient matched pairs of chemotherapy nave and resistant HGSOC and performed RNA sequencing. We noted transcriptional similarity between the patient-matched pairs of samples, but several recurrent transcriptional remodeling events were noted. Some fusions acquired in the chemotherapy-resistant HGSOC are found in HGSOC cell lines. One of these CCDC6-ANK3 is expressed in an HGSOC cell line and when knocked-down preliminary data shows decreased growth. We are currently examining the expression of these fusions in patients treated with neo-adjuvant chemotherapy pre and post therapy and examine the biologic function of prioritized RNA fusion events.
- Medicine and Medical Research