Establishment and characterization of a patient-derived solitary fibrous tumor/hemangiopericytoma cell line model

• Published in: Human cell : official journal of Human Cell Research Society Vol. 37; no. 1; pp. 310 - 322
• Main Authors: Lee, Jing Yi, Guan, Peiyong, Lim, Abner Herbert, Guo, Zexi, Li, Zhimei, Kok, Jessica Sook Ting, Lee, Elizabeth Chun Yong, Lim, Boon Yee, Kannan, Bavani, Loh, Jui Wan, Ng, Cedric Chuan-Young, Lim, Kah Suan, Teh, Bin Tean, Ko, Tun Kiat, Chan, Jason Yongsheng
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.01.2024; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; CD34 antigen; CD99 antigen; Cell Biology; Desmin; Drug development; Drug screening; EGR-1 protein; Genomes; Gynecology; Immunohistochemistry; Life Sciences; Oncology; Reproductive Medicine; Research Article; Soft tissue sarcoma; Stat6 protein; Stem Cells; Surgery; Transcriptomics; Tumors; Whole genome sequencing; Rare cancers; Epigenomics; Sarcoma; Targeted therapy; Next generation sequencing
• ISSN: 1749-0774; 0914-7470; 1749-0774
• DOI: 10.1007/s13577-023-01013-2

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 NAB2 exon3– STAT6 exon18 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. Graphical abstract