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@ARTICLE{Sievers:164298,
author = {P. Sievers$^*$ and M. Sill$^*$ and D. Schrimpf$^*$ and D.
Stichel$^*$ and D. Reuß$^*$ and D. Sturm$^*$ and J. Hench
and S. Frank and L. Krskova and A. Vicha and M. Zapotocky
and B. Bison and D. Castel and J. Grill and M.-A. Debily$^*$
and P. N. Harter$^*$ and M. Snuderl and C. M. Kramm and G.
Reifenberger$^*$ and A. Korshunov$^*$ and N. Jabado and P.
Wesseling and W. Wick$^*$ and D. A. Solomon and A. Perry and
T. S. Jacques and C. Jones and O. Witt$^*$ and S.
Pfister$^*$ and A. von Deimling$^*$ and D. Jones$^*$ and F.
Sahm$^*$},
title = {{A} subset of pediatric-type thalamic gliomas share a
distinct {DNA} methylation profile, {H}3{K}27me3 loss and
frequent alteration of {EGFR}.},
journal = {Neuro-Oncology},
volume = {23},
number = {1},
issn = {1523-5866},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2020-02381},
pages = {34-43},
year = {2021},
note = {2021 Jan 30;23(1):34-43 #EA:B360#LA:B300#},
abstract = {Malignant astrocytic gliomas in children show a remarkable
biological and clinical diversity. Small in-frame insertions
or missense mutations in the EGFR gene have recently been
identified in a distinct subset of pediatric-type bithalamic
gliomas with a unique DNA methylation pattern.Here, we
investigated an epigenetically homogeneous cohort of
malignant gliomas (n=58) distinct from other subtypes and
enriched for pediatric cases and thalamic location, in
comparison with this recently identified subtype of
pediatric bithalamic gliomas.EGFR gene amplification was
detected in 16/58 $(27\%)$ tumors, and missense mutations or
small in-frame insertions in EGFR were found in 20/30 tumors
with available sequencing data $(67\%;$ five of them
co-occurring with EGFR amplification). Additionally, eight
of the 30 tumors $(27\%)$ harbored an H3.1 or H3.3 K27M
mutation (six of them with a concomitant EGFR alteration).
All tumors tested showed loss of H3K27me3 staining, with
evidence of EZHIP overexpression in the H3 wildtype cases.
Although some tumors indeed showed a bithalamic growth
pattern, a significant proportion of tumors occurred in the
unilateral thalamus or in other (predominantly midline)
locations.Our findings present a distinct molecular class of
pediatric-type malignant gliomas largely overlapping with
the recently reported bithalamic gliomas characterized by
EGFR alteration, but additionally showing a broader spectrum
of EGFR alterations and tumor localization. Global H3K27me3
loss in this group appears to be mediated by either H3 K27
mutation or EZHIP overexpression. EGFR inhibition may
represent a potential therapeutic strategy in these highly
aggressive gliomas.},
cin = {HD01 / ED01 / B300 / B062 / B320 / B360},
ddc = {610},
cid = {I:(DE-He78)HD01-20160331 / I:(DE-He78)ED01-20160331 /
I:(DE-He78)B300-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)B320-20160331 / 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:33130881},
doi = {10.1093/neuonc/noaa251},
url = {https://inrepo02.dkfz.de/record/164298},
}