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@ARTICLE{Korshunov:167356,
author = {A. Korshunov$^*$ and K. Okonechnikov$^*$ and F.
Schmitt-Hoffner$^*$ and M. Ryzhova and F. Sahm$^*$ and D.
Stichel$^*$ and D. Schrimpf$^*$ and D. E. Reuss$^*$ and P.
Sievers$^*$ and A. K. Suwala$^*$ and E. Kumirova and O.
Zheludkova and A. Golanov and D. T. W. Jones$^*$ and S. M.
Pfister$^*$ and M. Kool$^*$ and A. von Deimling$^*$},
title = {{M}olecular analysis of pediatric {CNS}-{PNET} revealed
nosologic heterogeneity and potent diagnostic markers for
{CNS} neuroblastoma with {FOXR}2-activation.},
journal = {Acta Neuropathologica Communications},
volume = {9},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DKFZ-2021-00302},
pages = {20},
year = {2021},
note = {#EA:B300#LA:B300#},
abstract = {Primitive neuroectodermal tumors of the central nervous
system (CNS-PNETs) are highly malignant neoplasms posing
diagnostic challenge due to a lack of defining molecular
markers. CNS neuroblastoma with forkhead box R2 (FOXR2)
activation $(CNS_NBL)$ emerged as a distinct pediatric brain
tumor entity from a pool previously diagnosed as primitive
neuroectodermal tumors of the central nervous system
(CNS-PNETs). Current standard of identifying $CNS_NBL$
relies on molecular analysis. We set out to establish
immunohistochemical markers allowing safely distinguishing
$CNS_NBL$ from morphological mimics. To this aim we analyzed
a series of 84 brain tumors institutionally diagnosed as
CNS-PNET. As expected, epigenetic analysis revealed
different methylation groups corresponding to the (1)
CNS-NBL $(24\%),$ (2) glioblastoma IDH wild-type subclass
H3.3 G34 $(26\%),$ (3) glioblastoma IDH wild-type subclass
MYCN $(21\%)$ and (4) ependymoma with $RELA_C11orf95$ fusion
$(29\%)$ entities. Transcriptome analysis of this series
revealed a set of differentially expressed genes
distinguishing $CNS_NBL$ from its mimics. Based on
RNA-sequencing data we established SOX10 and ANKRD55
expression as genes discriminating $CNS_NBL$ from other
tumors exhibiting CNS-PNET. Immunohistochemical detection of
combined expression of SOX10 and ANKRD55 clearly identifies
$CNS_NBL$ discriminating them to other hemispheric CNS
neoplasms harboring 'PNET-like' microscopic appearance.
Owing the rarity of $CNS_NBL,$ a confirmation of the
elaborated diagnostic IHC algorithm will be necessary in
prospective patient series.},
keywords = {CNS-PNET (Other) / FOXR2-activation (Other) / Neuroblastoma
(Other) / SOX10 (Other)},
cin = {B300 / HD01 / B062 / B360},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B360-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33536079},
doi = {10.1186/s40478-021-01118-5},
url = {https://inrepo02.dkfz.de/record/167356},
}