Transcriptomic profiling and functional characterization of fusion genes in recurrent ovarian cancer
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1105407
Entities
People
- Adrian V Lee
Organizations
- University of Pittsburgh