%0 Journal Article
%A Imle, Roland
%A Blösel, Daniel
%A Kommoss, Felix Karl-Friedrich
%A Placke, Sara
%A Stutheit-Zhao, Eric
%A Blume, Christina
%A Lupar, Dmitry
%A Schmitt, Lukas
%A Winter, Claudia
%A Wagner, Lena
%A von Eicke, Malte
%A Walzer, Hannah
%A Förderer, Julia
%A Laier, Stephanie
%A Hertwig, Michael
%A Peterziel, Heike
%A Oehme, Ina
%A Scheuerman, Sophia
%A Seitz, Christian
%A Geyer, Florian H
%A Cidre-Aranaz, Florencia
%A Grünewald, Thomas
%A Vokuhl, Christian
%A Chudasama, Priya
%A Scholl, Claudia
%A Schmidt, Claudia
%A Günther, Patrick
%A Sill, Martin
%A Jones, Kevin B
%A Pfister, Stefan
%A Autry, Robert
%A Banito, Ana
%T Somatic gene delivery faithfully recapitulates a molecular spectrum of high-risk sarcomas.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DKFZ-2025-01243
%P 5283
%D 2025
%Z DKFZ-ZMBH Alliance /  #EA:B380#LA:B380#
%X 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.
%K Animals
%K Sarcoma: genetics
%K Sarcoma: pathology
%K Mice
%K Humans
%K Disease Models, Animal
%K Gene Transfer Techniques
%K Electroporation: methods
%K Mice, Transgenic
%K Female
%K Mice, Inbred C57BL
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40523919
%2 pmc:PMC12170903
%R 10.1038/s41467-025-60519-5
%U https://inrepo02.dkfz.de/record/302111