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@ARTICLE{Harter:126670,
author = {P. Harter$^*$ and P. Baumgarten and J. Zinke and K.
Schilling and S. Baader and A.-K. Hartmetz and J.
Schittenhelm and R. Beschorner and S. Liebner$^*$ and D.
Schulte and K.-H. Plate$^*$ and P. Gutwein and A.
Korshunov$^*$ and S. Pfister$^*$ and D. Jones$^*$ and K.
Doberstein$^*$ and M. Mittelbronn$^*$},
title = {{P}aired box gene 8 ({PAX}8) expression is associated with
sonic hedgehog ({SHH})/wingless int ({WNT}) subtypes,
desmoplastic histology and patient survival in human
medulloblastomas.},
journal = {Neuropathology $\&$ applied neurobiology},
volume = {41},
number = {2},
issn = {0305-1846},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2017-02698},
pages = {165 - 179},
year = {2015},
abstract = {The paired box gene 8 (PAX8) plays crucial roles in organ
patterning and cellular differentiation during development
and tumorigenesis. Although its function is partly
understood in vertebrate development, there is poor data
concerning human central nervous system (CNS) development
and brain tumours.We investigated developing human
(n = 19) and mouse (n = 3) brains as well as
medulloblastomas (MBs) (n = 113) for PAX8 expression by
immunohistochemistry. Human MB cell lines were assessed for
PAX8 expression using polymerase chain reaction and
immunoblotting and analysed for growth and migration
following PAX8 knock-down by small interfering ribonucleic
acid (siRNA).PAX8 protein expression was associated with
germinal layers in human and murine forebrain and hindbrain
development. PAX8 expression significantly decreased over
time in the external granule cell layer but increased in the
internal granule cell layer. In MB subtypes, we observed an
association of PAX8 expression with sonic hedgehog (SHH) and
wingless int subtypes but not with group 3 and 4 MBs. Beyond
that, we detected high PAX8 levels in desmoplastic MB
subtypes. Univariate analyses revealed high PAX8 levels as a
prognostic factor associated with a significantly better
patient prognosis in human MB (overall survival: Log-Rank
P = 0.0404, Wilcoxon P = 0.0280; progression-free
survival: Log-Rank P = 0.0225; Wilcoxon P = 0.0136).
In vitro assays revealed increased proliferation and
migration of MB cell lines after PAX8 siRNA knock-down.In
summary, high PAX8 expression is linked to better prognosis
in MBs potentially by suppressing both proliferative and
migratory properties of MB cells. The distinct
spatio-temporal expression pattern of PAX8 during brain
development might contribute to the understanding of
distinct MB subtype histogenesis.},
keywords = {Hedgehog Proteins (NLM Chemicals) / PAX8 Transcription
Factor (NLM Chemicals) / PAX8 protein, human (NLM Chemicals)
/ Paired Box Transcription Factors (NLM Chemicals) / RNA,
Small Interfering (NLM Chemicals) / SHH protein, human (NLM
Chemicals) / Wnt Proteins (NLM Chemicals)},
cin = {L101 / L501 / B062 / G380},
ddc = {610},
cid = {I:(DE-He78)L101-20160331 / I:(DE-He78)L501-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)G380-20160331},
pnm = {319H - Addenda (POF3-319H)},
pid = {G:(DE-HGF)POF3-319H},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25287489},
doi = {10.1111/nan.12186},
url = {https://inrepo02.dkfz.de/record/126670},
}