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@ARTICLE{Beck:301587,
author = {A. Beck and L. Gabler-Pamer and G. Alencastro Veiga
Cruzeiro and S. Lambo$^*$ and B. Englinger and M. L. Shaw
and O. A. Hack and I. Liu and R. D. Haase and C. A. O. de
Biagi and A. Baumgartner and A. D. Nascimento Silva and M.
Klenner and P. S. Freidel and J. Herms and L. von
Baumgarten$^*$ and J. C. Tonn$^*$ and N. Thon$^*$ and K.
Bruckner and S. Madlener and L. Mayr and D. Senfter and A.
Peyrl and I. Slavc and D. Lötsch and C. Dorfer and R.
Geyregger and N. Amberg and C. Haberler and N. Mack$^*$ and
B. Schwalm$^*$ and S. Pfister$^*$ and A. Korshunov$^*$ and
L. C. Baird and E. Yang and S. N. Chi and S. Alexandrescu
and J. Gojo and M. Kool$^*$ and V. Hovestadt and M. G.
Filbin},
title = {{C}ellular hierarchies of embryonal tumors with
multilayered rosettes are shaped by oncogenic micro{RNA}s
and receptor-ligand interactions.},
journal = {Nature cancer},
volume = {6},
number = {6},
issn = {2662-1347},
address = {London},
publisher = {Nature Research},
reportid = {DKFZ-2025-01095},
pages = {1035-1055},
year = {2025},
note = {#LA:B062# / 2025 Jun;6(6):1035-1055},
abstract = {Embryonal tumor with multilayered rosettes (ETMR) is a
pediatric brain tumor with dismal prognosis. Characteristic
alterations of the chromosome 19 microRNA cluster (C19MC)
are observed in most ETMR; however, the ramifications of
C19MC activation and the complex cellular architecture of
ETMR remain understudied. Here we analyze 11 ETMR samples
from patients using single-cell transcriptomics and
multiplexed spatial imaging. We reveal a spatially distinct
cellular hierarchy that spans highly proliferative neural
stem-like cells and more differentiated neuron-like cells.
C19MC is predominantly expressed in stem-like cells and
controls a transcriptional network governing stemness and
lineage commitment, as resolved by genome-wide analysis of
microRNA-mRNA binding. Systematic analysis of
receptor-ligand interactions between malignant cell types
reveals fibroblast growth factor receptor and Notch
signaling as oncogenic pathways that can be successfully
targeted in preclinical models and in one patient with ETMR.
Our study provides fundamental insights into ETMR
pathobiology and a powerful rationale for more effective
targeted therapies.},
cin = {B062 / HD01 / B300 / MU01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B300-20160331 / I:(DE-He78)MU01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40419763},
doi = {10.1038/s43018-025-00964-9},
url = {https://inrepo02.dkfz.de/record/301587},
}