Establishment and characterization of a patient-derived solitary fibrous tumor/hemangiopericytoma cell line model.
Jing Yi LeePeiyong GuanAbner Herbert LimZexi GuoZhimei LiJessica Sook Ting KokElizabeth Chun Yong LeeBoon Yee LimBavani KannanJui Wan LohCedric Chuan-Young NgKah Suan LimBin Tean TehTun Kiat KoJason Yongsheng ChanPublished in: Human cell (2023)
Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma harboring 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. Immunohistochemistry profiles of the PDC was consistent with the patient's tumor sample (CD99+/CD34+/desmin-). RNA sequencing, followed by Sanger sequencing confirmed the pathognomonic NAB2exon3-STAT6exon18 fusion in both the PDC and the original tumor. Transcriptomic data showed strong enrichment for oncogenic pathways (epithelial-mesenchymal transition, FGF, EGR1 and TGFβ signaling pathways) in the tumor. Whole genome sequencing identified potentially pathogenic somatic variants such as MAGEA10 and ABCA2. Among a panel of 14 targeted agents screened, dasatinib was identified to be the most potent small molecule inhibitor against the PDC (IC 50 , 473 nM), followed by osimertinib (IC 50 , 730 nM) and sunitinib (IC 50 , 1765 nM). Methylation profiling of the tumor suggests that this specific variant of SFT/HPC could lead to genome-wide hypomethylation. In conclusion, we established a novel PDC model of SFT/HPC with comprehensive characterization of its genomic, epigenomic and transcriptomic landscape, which can facilitate future preclinical studies of SFT/HPC, such as in vitro drug screening and in vivo drug testing.
Keyphrases
- single cell
- genome wide
- epithelial mesenchymal transition
- small molecule
- copy number
- photodynamic therapy
- dna methylation
- cell proliferation
- stem cells
- signaling pathway
- machine learning
- gene expression
- emergency department
- drug delivery
- adverse drug
- cancer therapy
- bone marrow
- endoplasmic reticulum stress
- smoking cessation
- data analysis