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<p>Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma characterized by high recurrence rates and the development of resistance to imatinib. The scarcity of preclinical models hinders research into DFSP pathogenesis and the development of novel therapeutic strategies. In this study, we established and characterized a novel DFSP cell line, designated DFSP-DPH1, derived from a 47-year-old male patient with an abdominal tumor. Comprehensive characterization confirmed that DFSP-DPH1 retains key features of the original tumor, including the fibroblast-like spindle morphology and expression of diagnostic markers CD34 and vimentin, with absence of factor XIIIa. Short tandem repeat profiling confirmed the cell line's origin and excluded cross-contamination. Sanger sequencing revealed a <i>COL1A1</i> exon 46-<i>PDGFB</i> exon 2 fusion transcript, a breakpoint not previously reported in established DFSP cell lines. Functionally, DFSP-DPH1 exhibits robust proliferative capacity, forms three-dimensional spheroids under anchorage-independent conditions, and demonstrates significant migratory and invasive capabilities. Drug sensitivity screening of a panel of 48 PDGFR inhibitors confirmed its resistance to imatinib and identified several compounds with superior efficacy compared to imatinib. Transcriptomic analysis confirmed the dominance of the <i>COL1A1::PDGFB</i> fusion transcript and revealed enrichment of pathways related to cancer, viral infection, and neuroactive ligand–receptor interaction. This novel imatinib-resistant DFSP cell line, DFSP-DPH1 provides a valuable preclinical model for investigating the molecular mechanisms underlying DFSP pathogenesis, drug resistance, and tumor progression, and for developing and evaluating novel therapeutic strategies.</p>

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Establishment and characterization of a novel imatinib-resistant dermatofibrosarcoma protuberans cell line, DFSP-DPH1

  • 期刊论文

  • 发表日期：

    2025年11月14日

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  • Hao Jiang,
  • Kunqian He,
  • Danli Li,
  • Fengjun Zhu,
  • Yuan Ren,
  • Xinying Li,
  • Yuanyuan Wang,
  • Junbo Zhang,
  • Yuangang Lu

摘要

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma characterized by high recurrence rates and the development of resistance to imatinib. The scarcity of preclinical models hinders research into DFSP pathogenesis and the development of novel therapeutic strategies. In this study, we established and characterized a novel DFSP cell line, designated DFSP-DPH1, derived from a 47-year-old male patient with an abdominal tumor. Comprehensive characterization confirmed that DFSP-DPH1 retains key features of the original tumor, including the fibroblast-like spindle morphology and expression of diagnostic markers CD34 and vimentin, with absence of factor XIIIa. Short tandem repeat profiling confirmed the cell line's origin and excluded cross-contamination. Sanger sequencing revealed a COL1A1 exon 46-PDGFB exon 2 fusion transcript, a breakpoint not previously reported in established DFSP cell lines. Functionally, DFSP-DPH1 exhibits robust proliferative capacity, forms three-dimensional spheroids under anchorage-independent conditions, and demonstrates significant migratory and invasive capabilities. Drug sensitivity screening of a panel of 48 PDGFR inhibitors confirmed its resistance to imatinib and identified several compounds with superior efficacy compared to imatinib. Transcriptomic analysis confirmed the dominance of the COL1A1::PDGFB fusion transcript and revealed enrichment of pathways related to cancer, viral infection, and neuroactive ligand–receptor interaction. This novel imatinib-resistant DFSP cell line, DFSP-DPH1 provides a valuable preclinical model for investigating the molecular mechanisms underlying DFSP pathogenesis, drug resistance, and tumor progression, and for developing and evaluating novel therapeutic strategies.