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@ARTICLE{Sievers:136812,
author = {P. Sievers$^*$ and D. Stichel$^*$ and D. Schrimpf$^*$ and
F. Sahm$^*$ and C. Koelsche$^*$ and D. E. Reuss$^*$ and A.
K. Wefers$^*$ and A. Reinhardt$^*$ and K. Huang$^*$ and A.
Ebrahimi$^*$ and Y. Hou and K. Pajtler$^*$ and S.
Pfister$^*$ and M. Hasselblatt and W. Stummer and U. Schick
and C. Hartmann and C. Hagel and O. Staszewski and G.
Reifenberger$^*$ and R. Beschorner and R. Coras and K.
Keyvani and P. Kohlhof and F. Diomedi-Camassei and C.
Herold-Mende and F. Giangaspero and E. Rushing and C.
Giannini and A. Korshunov$^*$ and D. Jones$^*$ and A. von
Deimling$^*$},
title = {{FGFR}1:{TACC}1 fusion is a frequent event in molecularly
defined extraventricular neurocytoma.},
journal = {Acta neuropathologica},
volume = {136},
number = {2},
issn = {1432-0533},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2018-01250},
pages = {293 - 302},
year = {2018},
abstract = {Extraventricular neurocytoma (EVN) is a rare primary brain
tumor occurring in brain parenchyma outside the ventricular
system. Histopathological characteristics resemble those of
central neurocytoma but exhibit a wider morphologic
spectrum. Accurate diagnosis of these histologically
heterogeneous tumors is often challenging because of the
overlapping morphological features and the lack of defining
molecular markers. Here, we explored the molecular landscape
of 40 tumors diagnosed histologically as EVN by
investigating copy number profiles and DNA methylation array
data. DNA methylation profiles were compared with those of
relevant differential diagnoses of EVN and with a broader
spectrum of diverse brain tumor entities. Based on this, our
tumor cohort segregated into different groups. While a large
fraction (n = 22) formed a separate epigenetic group
clearly distinct from established DNA methylation profiles
of other entities, a subset (n = 14) of histologically
diagnosed EVN grouped with clusters of other defined
entities. Three cases formed a small group close to but
separated from the epigenetically distinct EVN cases, and
one sample clustered with non-neoplastic brain tissue. Four
additional samples originally diagnosed otherwise were found
to molecularly resemble EVN. Thus, our results highlight a
distinct DNA methylation pattern for the majority of tumors
diagnosed as EVN, but also indicate that approximately
one third of morphological diagnoses of EVN epigenetically
correspond to other brain tumor entities. Copy number
analysis and confirmation through RNA sequencing revealed
FGFR1-TACC1 fusion as a distinctive, recurrent feature
within the EVN methylation group $(60\%),$ in addition to a
small number of other FGFR rearrangements $(13\%).$ In
conclusion, our data demonstrate a specific epigenetic
signature of EVN suitable for characterization of these
tumors as a molecularly distinct entity, and reveal a high
frequency of potentially druggable FGFR pathway activation
in this tumor group.},
cin = {G380 / L101 / B062 / L401 / B360},
ddc = {610},
cid = {I:(DE-He78)G380-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)L401-20160331 /
I:(DE-He78)B360-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29978331},
doi = {10.1007/s00401-018-1882-3},
url = {https://inrepo02.dkfz.de/record/136812},
}