Transcriptomic Profiling and Functional Characterization of Fusion Genes in Recurrent Ovarian Cancer
Technical Report,15 Aug 2016,14 Aug 2017
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. In the first year of this proposal we have assembled a cohort of 18 patient matched pairs of chemotherapy nave and resistant HGSOC and performed RNA sequencing. Every case showed acquisition of RNA fusions average of 7 in the recurrent disease. Some fusions have biological functions in drug resistance, and some are found in HGSOC cell lines. We noted transcriptional similarity between the patient-matched pairs of samples, but several recurrent transcriptional remodeling events were noted. For the next year we will validate the clinical significance and biologic function of prioritized RNA fusion events.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology