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@ARTICLE{Hou:143592,
author = {Y. Hou and J. Pinheiro and F. Sahm$^*$ and D. E. Reuss$^*$
and D. Schrimpf$^*$ and D. Stichel$^*$ and B. Casalini$^*$
and C. Koelsche and P. Sievers$^*$ and A. K. Wefers$^*$ and
A. Reinhardt$^*$ and A. Ebrahimi$^*$ and F.
Fernández-Klett$^*$ and S. Pusch$^*$ and J. Meier and L.
Schweizer$^*$ and W. Paulus and M. Prinz and C. Hartmann and
K. H. Plate$^*$ and G. Reifenberger and T. Pietsch and P.
Varlet and M. Pagès and U. Schüller and D. Scheie and K.
de Stricker and S. Frank and J. Hench and B. Pollo and S.
Brandner and A. Unterberg and S. M. Pfister$^*$ and D. T. W.
Jones$^*$ and A. Korshunov$^*$ and W. Wick$^*$ and D.
Capper$^*$ and I. Blümcke and A. von Deimling$^*$ and L.
Bertero},
title = {{P}apillary glioneuronal tumor ({PGNT}) exhibits a
characteristic methylation profile and fusions involving
{PRKCA}.},
journal = {Acta neuropathologica},
volume = {137},
number = {5},
issn = {1432-0533},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2019-01172},
pages = {837 - 846},
year = {2019},
abstract = {Papillary glioneuronal tumor (PGNT) is a WHO-defined brain
tumor entity that poses a major diagnostic challenge.
Recently, SLC44A1-PRKCA fusions have been described in PGNT.
We subjected 28 brain tumors from different institutions
histologically diagnosed as PGNT to molecular and
morphological analysis. Array-based methylation analysis
revealed that 17/28 tumors exhibited methylation profiles
typical for other tumor entities, mostly dysembryoplastic
neuroepithelial tumor and hemispheric pilocytic astrocytoma.
Conversely, 11/28 tumors exhibited a unique profile, thus
constituting a distinct methylation class PGNT. By screening
the extended Heidelberg cohort containing over 25,000 CNS
tumors, we identified three additional tumors belonging to
this methylation cluster but originally histologically
diagnosed otherwise. RNA sequencing for the detection of
SLC44A1-PRKCA fusions could be performed on 19 of the
tumors, 10 of them belonging to the methylation class PGNT.
In two additional cases, SLC44A1-PRKCA fusions were
confirmed by FISH. We detected fusions involving PRKCA in
all cases of this methylation class with material available
for analyses: the canonical SLC44A1-PRKCA fusion was
observed in 11/12 tumors, while the remaining case exhibited
a NOTCH1-PRKCA fusion. Neither of the fusions was found in
the tumors belonging to other methylation classes. Our
results point towards a high misclassification rate of the
morphological diagnosis PGNT and clearly demonstrate the
necessity of molecular analyses. PRKCA fusions are highly
diagnostic for PGNT, and detection by RNA sequencing enables
the identification of rare fusion partners. Methylation
analysis recognizes a unique methylation class PGNT
irrespective of the nature of the PRKCA fusion.},
cin = {B300 / B062 / B320 / B360 / L101 / L201 / L501 / L401},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)B320-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)L101-20160331 / I:(DE-He78)L201-20160331 /
I:(DE-He78)L501-20160331 / I:(DE-He78)L401-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30759284},
doi = {10.1007/s00401-019-01969-2},
url = {https://inrepo02.dkfz.de/record/143592},
}