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

Autor: Lee JY; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore.; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore., Guan P; Agency for Science, Technology and Research (A*STAR), Genome Institute of Singapore, Singapore, Singapore., Lim AH; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Guo Z; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Li Z; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Kok JST; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore., Lee ECY; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Lim BY; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Kannan B; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Loh JW; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Ng CC; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore.; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore., Lim KS; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Teh BT; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore.; Agency for Science, Technology and Research (A*STAR), Genome Institute of Singapore, Singapore, Singapore.; Duke-NUS Medical School, Oncology Academic Clinical Program, Singapore, Singapore., Ko TK; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore., Chan JY; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore. jason.chan.y.s@nccs.com.sg.; Duke-NUS Medical School, Oncology Academic Clinical Program, Singapore, Singapore. jason.chan.y.s@nccs.com.sg.; Division of Medical Oncology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore, 168583, Singapore. jason.chan.y.s@nccs.com.sg.
Jazyk: angličtina
Zdroj: Human cell [Hum Cell] 2024 Jan; Vol. 37 (1), pp. 310-322. Date of Electronic Publication: 2023 Dec 09.
DOI: 10.1007/s13577-023-01013-2
Abstrakt: 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.
(© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)
Databáze: MEDLINE
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