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@ARTICLE{Imle:302111,
author = {R. Imle$^*$ and D. Blösel$^*$ and F. K. Kommoss$^*$ and S.
Placke$^*$ and E. Stutheit-Zhao$^*$ and C. Blume$^*$ and D.
Lupar$^*$ and L. Schmitt$^*$ and C. Winter$^*$ and L.
Wagner$^*$ and M. von Eicke$^*$ and H. Walzer$^*$ and J.
Förderer$^*$ and S. Laier$^*$ and M. Hertwig$^*$ and H.
Peterziel$^*$ and I. Oehme$^*$ and S. Scheuerman$^*$ and C.
Seitz$^*$ and F. H. Geyer$^*$ and F. Cidre-Aranaz$^*$ and T.
Grünewald$^*$ and C. Vokuhl and P. Chudasama$^*$ and C.
Scholl$^*$ and C. Schmidt$^*$ and P. Günther and M.
Sill$^*$ and K. B. Jones and S. Pfister$^*$ and R. Autry$^*$
and A. Banito$^*$},
title = {{S}omatic gene delivery faithfully recapitulates a
molecular spectrum of high-risk sarcomas.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01243},
pages = {5283},
year = {2025},
note = {DKFZ-ZMBH Alliance / #EA:B380#LA:B380#},
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.},
keywords = {Animals / Sarcoma: genetics / Sarcoma: pathology / Mice /
Humans / Disease Models, Animal / Gene Transfer Techniques /
Electroporation: methods / Mice, Transgenic / Female / Mice,
Inbred C57BL},
cin = {B380 / B062 / HD01 / B300 / W420 / A190 / B310 / B410 /
B390 / B290 / W210},
ddc = {500},
cid = {I:(DE-He78)B380-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)W420-20160331 / I:(DE-He78)A190-20160331 /
I:(DE-He78)B310-20160331 / I:(DE-He78)B410-20160331 /
I:(DE-He78)B390-20160331 / I:(DE-He78)B290-20160331 /
I:(DE-He78)W210-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40523919},
pmc = {pmc:PMC12170903},
doi = {10.1038/s41467-025-60519-5},
url = {https://inrepo02.dkfz.de/record/302111},
}