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@ARTICLE{Paassen:275262,
author = {I. Paassen and J. Williams and C. Ríos Arceo and F.
Ringnalda and K. S. Mercer and J. L. Buhl and N. Moreno and
A. Federico$^*$ and N. E. Franke and M. Kranendonk and S. A.
Upadhyaya and K. Kerl and M. van de Wetering and H. Clevers
and M. Kool$^*$ and E. W. Hoving and M. F. Roussel and J.
Drost},
title = {{A}typical teratoid/rhabdoid tumoroids reveal
subgroup-specific drug vulnerabilities.},
journal = {Oncogene},
volume = {42},
number = {20},
issn = {0950-9232},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2023-00709},
pages = {1661-1671},
year = {2023},
note = {2023 May;42(20):1661-1671},
abstract = {Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare,
but aggressive pediatric brain tumor entity. They are
genetically defined by alterations in the SWI/SNF chromatin
remodeling complex members SMARCB1 or SMARCA4. ATRTs can be
further classified in different molecular subgroups based on
their epigenetic profiles. Although recent studies suggest
that the different subgroups have distinct clinical
features, subgroup-specific treatment regimens have not been
developed thus far. This is hampered by the lack of
pre-clinical in vitro models representative of the different
molecular subgroups. Here, we describe the establishment of
ATRT tumoroid models from the ATRT-MYC and ATRT-SHH
subgroups. We demonstrate that ATRT tumoroids retain
subgroup-specific epigenetic and gene expression profiles.
High throughput drug screens on our ATRT tumoroids revealed
distinct drug sensitivities between and within ATRT-MYC and
ATRT-SHH subgroups. Whereas ATRT-MYC universally displayed
high sensitivity to multi-targeted tyrosine kinase
inhibitors, ATRT-SHH showed a more heterogeneous response
with a subset showing high sensitivity to NOTCH inhibitors,
which corresponded to high expression of NOTCH receptors.
Our ATRT tumoroids represent the first pediatric brain tumor
organoid model, providing a representative pre-clinical
model which enables the development of subgroup-specific
therapies.},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37020038},
doi = {10.1038/s41388-023-02681-y},
url = {https://inrepo02.dkfz.de/record/275262},
}