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Establishment and characterization of a patient-derived solitary fibrous tumor/hemangiopericytoma cell line model.
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.
Affiliation
  • Lee JY; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore.
  • Guan P; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore.
  • Lim AH; Agency for Science, Technology and Research (A*STAR), Genome Institute of 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; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore.
  • Lee ECY; Laboratory of Cancer Epigenome, Division of Medical Sciences, 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.
  • 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.
  • Ko TK; Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, Singapore.
  • Chan JY; Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore.
Hum Cell ; 37(1): 310-322, 2024 Jan.
Article in En | MEDLINE | ID: mdl-38070062
ABSTRACT
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 TGFß 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 (IC50, 473 nM), followed by osimertinib (IC50, 730 nM) and sunitinib (IC50, 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Solitary Fibrous Tumors / Hemangiopericytoma Limits: Humans Language: En Journal: Hum Cell Year: 2024 Document type: Article Affiliation country: Singapore

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Solitary Fibrous Tumors / Hemangiopericytoma Limits: Humans Language: En Journal: Hum Cell Year: 2024 Document type: Article Affiliation country: Singapore