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@ARTICLE{Schwab:300144,
      author       = {H. Schwab and M. Kerkhoff$^*$ and P. Plaumann$^*$ and S.
                      Collaud and U. Dirksen$^*$ and D. Theegarten and T. Herold
                      and S. Kalbourtzis and S. Bölükbas and B. Hegedüs and L.
                      Hegedüs},
      title        = {{C}haracterization of a novel sarcoma cell line with an
                      {EWSR}1::{POU}2{AF}3 fusion.},
      journal      = {Pathology $\&$ oncology research},
      volume       = {31},
      issn         = {1219-4956},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-00635},
      pages        = {1611986},
      year         = {2025},
      abstract     = {Sarcomas with an EWSR1::POU2AF3(COLCA2) fusion are a very
                      recently described entity of preferentially sinonasal origin
                      and with undifferentiated round/spindle cell morphology. We
                      established a novel cell line (PF1095) carrying a
                      EWSR1::POU2AF3 fusion from the malignant pleural effusion of
                      a 25-year-old sarcoma patient. The patient was first
                      diagnosed with poorly differentiated neuroendocrine
                      carcinoma based on tumor cell morphology and positivity to
                      markers such as EMA, synaptophysin, and CD56. Later, the
                      EWSR1 translocation was identified in the tumor cells with
                      unknown partners and the patient received chemotherapy
                      according to the Ewing 2008 protocol in combination with
                      surgery and proton beam radiotherapy. At the time of cell
                      line establishment, the disease progressed to pleural
                      sarcomatosis with pleural effusion. In the cell line, we
                      identified POU2AF3 as a fusion partner of EWSR1 and a TP53
                      frameshift deletion. Next, we determined the sensitivity of
                      PF1095 cells to the currently approved chemotherapies in
                      comparison to two conventional Ewing sarcoma lines (EW-7 and
                      MHH-ES1) with the two most frequent EWSR::FLI1 fusions.
                      Finally, we tested potential new combination therapies. We
                      performed cell viability, proliferation, and cell cycle
                      assays. We found that the proliferation rate of PF1095 cells
                      was much slower than the EWSR1::FLI1 fusion lines and they
                      also had a lower sensitivity to both irinotecan and
                      doxorubicin treatment. Expression level of SLFN11, a
                      predictor of sensitivity to DNA damaging agents, was also
                      lower in PF1095 cells. Combination treatment with the PARP
                      inhibitors olaparib and irinotecan or doxorubicin
                      synergistically reduced cell viability and induced cell
                      death and cell cycle arrest. This unique cell model provides
                      an opportunity to test therapeutic approaches preclinically
                      for this novel and aggressive sarcoma entity.},
      keywords     = {Humans / Oncogene Proteins, Fusion: genetics / RNA-Binding
                      Protein EWS: genetics / Adult / Sarcoma: genetics / Sarcoma:
                      pathology / Cell Line, Tumor / Cell Proliferation / Male /
                      EWSR1 (Other) / POU2AF3 (Other) / chemotherapy (Other) /
                      patient derived cell line (Other) / sarcoma (Other) /
                      Oncogene Proteins, Fusion (NLM Chemicals) / RNA-Binding
                      Protein EWS (NLM Chemicals) / EWSR1 protein, human (NLM
                      Chemicals)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40134582},
      pmc          = {pmc:PMC11932835},
      doi          = {10.3389/pore.2025.1611986},
      url          = {https://inrepo02.dkfz.de/record/300144},
}