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@ARTICLE{Kawauchi:128633,
author = {D. Kawauchi$^*$ and R. J. Ogg and L. Liu and D. J. H. Shih
and D. Finkelstein and B. L. Murphy and J. E. Rehg and A.
Korshunov$^*$ and C. Calabrese and F. Zindy and T. Phoenix
and Y. Kawaguchi and J. Gronych$^*$ and R. J. Gilbertson and
P. Lichter$^*$ and A. Gajjar and M. Kool$^*$ and P. A.
Northcott and S. Pfister$^*$ and M. F. Roussel},
title = {{N}ovel {MYC}-driven medulloblastoma models from multiple
embryonic cerebellar cells.},
journal = {Oncogene},
volume = {36},
number = {37},
issn = {1476-5594},
address = {Basingstoke},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2017-04649},
pages = {5231 - 5242},
year = {2017},
abstract = {Group3 medulloblastoma (MBG3) that predominantly occur in
young children are usually associated with MYC amplification
and/or overexpression, frequent metastasis and a dismal
prognosis. Physiologically relevant MBG3 models are
currently lacking, making inferences related to their
cellular origin thus far limited. Using in utero
electroporation, we here report that MBG3 mouse models can
be developed in situ from different multipotent embryonic
cerebellar progenitor cells via conditional expression of
Myc and loss of Trp53 function in several Cre driver mouse
lines. The Blbp-Cre driver that targets embryonic neural
progenitors induced tumors exhibiting a
large-cell/anaplastic histopathology adjacent to the fourth
ventricle, recapitulating human MBG3. Enforced co-expression
of luciferase together with Myc and a dominant-negative form
of Trp53 revealed that GABAergic neuronal progenitors as
well as cerebellar granule cells give rise to MBG3 with
their distinct growth kinetics. Cross-species gene
expression analysis revealed that these novel MBG3 models
shared molecular characteristics with human MBG3,
irrespective of their cellular origin. We here developed
MBG3 mouse models in their physiological environment and we
show that oncogenic insults drive this MB subgroup in
different cerebellar lineages rather than in a specific cell
of origin.},
keywords = {MYC protein, human (NLM Chemicals) / Myc protein, mouse
(NLM Chemicals) / Proto-Oncogene Proteins c-myc (NLM
Chemicals)},
cin = {B062 / G380 / B060},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)G380-20160331 /
I:(DE-He78)B060-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28504719},
pmc = {pmc:PMC5605674},
doi = {10.1038/onc.2017.110},
url = {https://inrepo02.dkfz.de/record/128633},
}