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| Home > Publications database > Somatic gene delivery faithfully recapitulates a molecular spectrum of high-risk sarcomas. |
| Home > Publications database > Somatic gene delivery faithfully recapitulates a molecular spectrum of high-risk sarcomas. |
| Journal Article | DKFZ-2025-01243 |
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2025
Springer Nature
[London]
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Please use a persistent id in citations: doi:10.1038/s41467-025-60519-5
Abstract: A major challenge hampering therapeutic advancements for high-risk sarcoma patients is the broad spectrum of molecularly distinct sarcoma types and the corresponding lack of suitable model systems. Here we describe the development of a genetically-controlled, yet versatile mouse modeling platform allowing delivery of different genetic lesions by muscle electroporation (EPO) in wildtype mice. This EPO-GEMM (EPO-based genetically engineered mouse model) platform allows the generation of ten genetically distinct sarcomas on an isogenic background, including the first model of ETV6::NTRK3-driven sarcoma. Comprehensive histological and molecular profiling reveals that this mouse sarcoma cohort recapitulates a spectrum of molecularly diverse sarcomas with gene fusions acting as major determinants of sarcoma biology. Integrative cross-species analyses show faithful recapitulation of human sarcoma subtypes, including expression of relevant immunotherapy targets. Comparison of syngeneic allografting methods enables reliable preservation and scalability of sarcoma-EPO-GEMMs for preclinical treatment trials, such as NTRK inhibitor therapy in an immunocompetent background.
Keyword(s): Animals (MeSH) ; Sarcoma: genetics (MeSH) ; Sarcoma: pathology (MeSH) ; Mice (MeSH) ; Humans (MeSH) ; Disease Models, Animal (MeSH) ; Gene Transfer Techniques (MeSH) ; Electroporation: methods (MeSH) ; Mice, Transgenic (MeSH) ; Female (MeSH) ; Mice, Inbred C57BL (MeSH)
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