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| 001 | 302111 | ||
| 005 | 20251002115236.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-025-60519-5 |2 doi |
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| 041 | _ | _ | |a English |
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| 100 | 1 | _ | |a Imle, Roland |0 P:(DE-He78)3c021852cf94cb29825e65baa82ed54b |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Somatic gene delivery faithfully recapitulates a molecular spectrum of high-risk sarcomas. |
| 260 | _ | _ | |a [London] |c 2025 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1750253028_2011 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 520 | _ | _ | |a 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. |
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| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Sarcoma: genetics |2 MeSH |
| 650 | _ | 2 | |a Sarcoma: pathology |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Disease Models, Animal |2 MeSH |
| 650 | _ | 2 | |a Gene Transfer Techniques |2 MeSH |
| 650 | _ | 2 | |a Electroporation: methods |2 MeSH |
| 650 | _ | 2 | |a Mice, Transgenic |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Mice, Inbred C57BL |2 MeSH |
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| 773 | _ | _ | |a 10.1038/s41467-025-60519-5 |g Vol. 16, no. 1, p. 5283 |0 PERI:(DE-600)2553671-0 |n 1 |p 5283 |t Nature Communications |v 16 |y 2025 |x 2041-1723 |
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