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@ARTICLE{Schmiester:305618,
      author       = {M. Schmiester and A. Freytag and B. Gillissen and E.
                      Sträng and R. Hablesreiter and A. Richter and J. K.
                      Striefler and M. von Laffert and M. Hummel and A. Jarosch
                      and D. Kaul and P. Ghadjar and R. Öllinger and D. Rau and
                      S. Märdian and L. Bullinger$^*$ and A. Dolnik and A.
                      Flörcken$^*$},
      title        = {{G}enomic evolution of high-risk soft tissue sarcomas under
                      thermo- and chemotherapeutic selection pressure.},
      journal      = {International journal of hyperthermia and thermal
                      therapies},
      volume       = {42},
      number       = {1},
      issn         = {0265-6736},
      address      = {London},
      publisher    = {Informa UK Limited},
      reportid     = {DKFZ-2025-02266},
      pages        = {2573753},
      year         = {2025},
      note         = {ISSN 1464-5157},
      abstract     = {The integration of regional hyperthermia into the
                      multimodal treatment of patients with localized high-risk
                      soft tissue sarcomas has been shown to improve overall
                      survival. However, specific effects on the tumors' genetic
                      makeup and biology are largely unknown. Since clonal
                      selection of malignant cells capable of thermoresistance
                      might contribute to disease progression, a better
                      understanding of the induced tumor evolution could inform
                      strategies for improving treatment efficacy.We performed
                      whole exome sequencing on paired sarcoma samples obtained
                      before and after treatment with chemotherapy combined with
                      regional hyperthermia (n = 12 patients; n = 9 paired
                      samples, n = 3 post-treatment only).Tumor evolution was
                      evident in all paired samples, with shifts in small- and
                      large-scale genomic alterations. Overall, these alterations
                      appeared tumor-specific, but recurrent mutations in histone
                      H3-modifying genes were found exclusively in
                      post-therapeutic samples.Our findings showcase the diversity
                      of genomic evolution patterns in sarcomas emerging under
                      combined thermo- and chemotherapeutic selection pressure,
                      indicating that treatment response may vary according to the
                      specific tumor composition. With previous studies linking
                      histone functions to heat stress response, the alterations
                      found in genes modifying H3 in our post-therapeutic cohort
                      provide biological evidence for synergy of chemotherapy
                      combined with regional hyperthermia in soft tissue
                      sarcomas.},
      keywords     = {Humans / Sarcoma: genetics / Sarcoma: therapy / Sarcoma:
                      drug therapy / Sarcoma: pathology / Female / Male / Middle
                      Aged / Hyperthermia, Induced: methods / Adult / Aged /
                      Genomics: methods / Soft tissue sarcoma (Other) / histone
                      H3.3 regulation (Other) / hyperthermia (Other) / tumor
                      evolution (Other) / whole exome sequencing (Other)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41186067},
      doi          = {10.1080/02656736.2025.2573753},
      url          = {https://inrepo02.dkfz.de/record/305618},
}