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@ARTICLE{Rhrich:130427,
author = {M. Röhrich$^*$ and C. Koelsche$^*$ and D. Schrimpf$^*$ and
D. Capper$^*$ and F. Sahm$^*$ and A. Kratz$^*$ and J.
Reuss$^*$ and V. Hovestadt$^*$ and D. Jones$^*$ and M.
Bewerunge-Hudler$^*$ and A. Becker and J. Weis and C. Mawrin
and M. Mittelbronn$^*$ and A. Perry and V.-F. Mautner and G.
Mechtersheimer and C. Hartmann and A. F. Okuducu and M. Arp
and M. Seiz-Rosenhagen and D. Hänggi and S. Heim and W.
Paulus and J. Schittenhelm and R. Ahmadi and C. Herold-Mende
and A. Unterberg and S. Pfister$^*$ and A. von Deimling$^*$
and D. E. Reuss$^*$},
title = {{M}ethylation-based classification of benign and malignant
peripheral nerve sheath tumors.},
journal = {Acta neuropathologica},
volume = {131},
number = {6},
issn = {1432-0533},
address = {Berlin},
publisher = {Springer},
reportid = {DKFZ-2017-05506},
pages = {877 - 887},
year = {2016},
abstract = {The vast majority of peripheral nerve sheath tumors derive
from the Schwann cell lineage and comprise diverse
histological entities ranging from benign schwannomas and
neurofibromas to high-grade malignant peripheral nerve
sheath tumors (MPNST), each with several variants. There is
increasing evidence for methylation profiling being able to
delineate biologically relevant tumor groups even within the
same cellular lineage. Therefore, we used DNA methylation
arrays for methylome- and chromosomal profile-based
characterization of 171 peripheral nerve sheath tumors. We
analyzed 28 conventional high-grade MPNST, three malignant
Triton tumors, six low-grade MPNST, four epithelioid MPNST,
33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform),
six atypical neurofibromas, 43 schwannomas (including 5 NF2
and 5 schwannomatosis associated cases), 11 cellular
schwannomas, 10 melanotic schwannomas, 7
neurofibroma/schwannoma hybrid tumors, 10 nerve sheath
myxomas and 10 ganglioneuromas. Schwannomas formed different
epigenomic subgroups including a vestibular schwannoma
subgroup. Cellular schwannomas were not distinct from
conventional schwannomas. Nerve sheath myxomas and
neurofibroma/schwannoma hybrid tumors were most similar to
schwannomas. Dermal, intraneural and plexiform neurofibromas
as well as ganglioneuromas all showed distinct methylation
profiles. Atypical neurofibromas and low-grade MPNST were
indistinguishable with a common methylation profile and
frequent losses of CDKN2A. Epigenomic analysis finds two
groups of conventional high-grade MPNST sharing a frequent
loss of neurofibromin. The larger of the two groups shows an
additional loss of trimethylation of histone H3 at lysine 27
(H3K27me3). The smaller one retains H3K27me3 and is found in
spinal locations. Sporadic MPNST with retained neurofibromin
expression did not form an epigenetic group and most cases
could be reclassified as cellular schwannomas or soft tissue
sarcomas. Widespread immunohistochemical loss of H3K27me3
was exclusively seen in MPNST of the main methylation
cluster, which defines it as an additional useful marker for
the differentiation of cellular schwannoma and MPNST.},
keywords = {Neurofibromin 1 (NLM Chemicals)},
cin = {E055 / G380 / B060 / B062 / W110 / L501 / L101},
ddc = {610},
cid = {I:(DE-He78)E055-20160331 / I:(DE-He78)G380-20160331 /
I:(DE-He78)B060-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)W110-20160331 / I:(DE-He78)L501-20160331 /
I:(DE-He78)L101-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26857854},
doi = {10.1007/s00401-016-1540-6},
url = {https://inrepo02.dkfz.de/record/130427},
}