(P 174) ESTABLISHMENT AND CHARACTERIZATION OF A PATIENT-DERIVED SOLITARY FIBROUS TUMOR/HEMANGIOPERICYTOMA CELL LINE MODEL

Objective: Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. Mechanistic studies and therapeutic development on SFT/HPC are impeded by scarcity and lack of system models. In this study, we established and characterized a novel SFT/HPC patient-derived cell line (PDC), SFT-S1, and screened for potential drug candidates that could be repurposed for the treatment of SFT/HPC.

Methods: Fresh tumor and adjacent normal tissues were obtained from a 39-year-old female patient who underwent an endoscopic left medial maxillectomy for a sino-nasal hemangiopericytoma. Morphological characterization using immunohistochemistry (IHC) was performed on both the PDC and primary tumor. Transcriptomic profiling (RNA-seq) and whole genome sequencing (WGS) were performed. A drug screen comprising of 14 small molecule inhibitors was conducted against the cell line and their IC50s were determined.

Results: The PDC was maintained in continuous passage for more than a year with no signs of senescence and was therefore considered immortalized. The cell-line had an estimated in vitro population doubling time of 2 weeks. IHC demonstrated diffuse strong membranous CD99 staining, negativity for desmin and heterogeneous CD34 staining, concordant in both the PDC and tumor tissue. RNA-seq analysis revealed presence of NAB2ex3-STAT6ex18 fusion, as well as strong enrichment for oncogenic-related pathways (epithelial-mesenchymal transition, FGF, EGR1 and TGFβ signalling pathways) in the tumor as compared to the matched normal tissue. Sanger sequencing confirmed the pathognomonic NAB2-STAT6 fusion in the tumor and PDC. WGS identified potentially pathogenic somatic variants (VAF>5%) such as MAGEA10 and ABCA2. Dasatinib was identified to be the most potent small molecule inhibitor against the PDC (IC50, 473 nM), followed by osimertinib (IC50, 730 nM) and sunitinib (IC50, 1765 nM).

Conclusion: In conclusion, we established a novel PDC model of SFT/HPC with comprehensive characterization of its genomic and transcriptomic landscape. Further studies are underway to understand mechanisms underlying the observed drug responses.

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