TY  - JOUR
AU  - Imle, Roland
AU  - Blösel, Daniel
AU  - Kommoss, Felix Karl-Friedrich
AU  - Placke, Sara
AU  - Stutheit-Zhao, Eric
AU  - Blume, Christina
AU  - Lupar, Dmitry
AU  - Schmitt, Lukas
AU  - Winter, Claudia
AU  - Wagner, Lena
AU  - von Eicke, Malte
AU  - Walzer, Hannah
AU  - Förderer, Julia
AU  - Laier, Stephanie
AU  - Hertwig, Michael
AU  - Peterziel, Heike
AU  - Oehme, Ina
AU  - Scheuerman, Sophia
AU  - Seitz, Christian
AU  - Geyer, Florian H
AU  - Cidre-Aranaz, Florencia
AU  - Grünewald, Thomas
AU  - Vokuhl, Christian
AU  - Chudasama, Priya
AU  - Scholl, Claudia
AU  - Schmidt, Claudia
AU  - Günther, Patrick
AU  - Sill, Martin
AU  - Jones, Kevin B
AU  - Pfister, Stefan
AU  - Autry, Robert
AU  - Banito, Ana
TI  - Somatic gene delivery faithfully recapitulates a molecular spectrum of high-risk sarcomas.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01243
SP  - 5283
PY  - 2025
N1  - DKFZ-ZMBH Alliance /  #EA:B380#LA:B380#
AB  - 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.
KW  - Animals
KW  - Sarcoma: genetics
KW  - Sarcoma: pathology
KW  - Mice
KW  - Humans
KW  - Disease Models, Animal
KW  - Gene Transfer Techniques
KW  - Electroporation: methods
KW  - Mice, Transgenic
KW  - Female
KW  - Mice, Inbred C57BL
LB  - PUB:(DE-HGF)16
C6  - pmid:40523919
C2  - pmc:PMC12170903
DO  - DOI:10.1038/s41467-025-60519-5
UR  - https://inrepo02.dkfz.de/record/302111
ER  -