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@ARTICLE{Pierce:148651,
author = {A. M. Pierce and D. A. Witt and A. M. Donson and A. Gilani
and B. Sanford and M. Sill$^*$ and B. Van Court and A.
Oweida and E. W. Prince and J. Steiner and E. Danis and K.
Dorris and T. Hankinson and M. H. Handler and K. L. Jones
and S. D. Karam and N. J. Serkova and R. Vibhakar and N. K.
Foreman and A. M. Griesinger},
title = {{E}stablishment of patient-derived orthotopic xenograft
model of 1q+ posterior fossa group {A} ependymoma.},
journal = {Neuro-Oncology},
volume = {21},
number = {12},
issn = {1523-5866},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2019-03189},
pages = {1540 - 1551},
year = {2019},
abstract = {Treatment for pediatric posterior fossa group A (PFA)
ependymoma with gain of chromosome 1q (1q+) has not improved
over the past decade owing partially to lack of clinically
relevant models. We described the first 2 1q+ PFA cell
lines, which have significantly enhanced our understanding
of PFA tumor biology and provided a tool to identify
specific 1q+ PFA therapies. However, cell lines do not
accurately replicate the tumor microenvironment. Our present
goal is to establish patient-derived xenograft (PDX) mouse
models.Disaggregated tumors from 2 1q+ PFA patients were
injected into the flanks of NSG mice. Flank tumors were then
transplanted into the fourth ventricle or lateral ventricle
of NSG mice. Characterization of intracranial tumors was
performed using imaging, histology, and
$bioinformatics.MAF-811_XC$ and $MAF-928_XC$ established
intracranially within the fourth ventricle and retained
histological, methylomic, and transcriptomic features of
primary patient tumors. We tested the feasibility of
treating PDX mice with fractionated radiation or
chemotherapy. Mice tolerated radiation despite significant
tumor burden, and follow-up imaging confirmed radiation can
reduce tumor size. Treatment with fluorouracil reduced tumor
size but did not appear to prolong $survival.MAF-811_XC$ and
$MAF-928_XC$ are novel, authentic, and reliable models for
studying 1q+ PFA in vivo. Given the successful response to
radiation, these models will be advantageous for testing
clinically relevant combination therapies to develop future
clinical trials for this high-risk subgroup of pediatric
ependymoma.},
cin = {B062},
ddc = {610},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31276586},
doi = {10.1093/neuonc/noz116},
url = {https://inrepo02.dkfz.de/record/148651},
}