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@ARTICLE{Suwala:168435,
author = {A. K. Suwala$^*$ and D. Stichel$^*$ and D. Schrimpf$^*$ and
S. L. N. Maas and M. Sill$^*$ and H. Dohmen and R. Banan and
A. Reinhardt$^*$ and P. Sievers$^*$ and F. Hinz$^*$ and M.
Blattner-Johnson$^*$ and C. Hartmann and L. Schweizer$^*$
and H. B. Boldt and B. W. Kristensen and J. Schittenhelm and
M. D. Wood and G. Chotard and R. Bjergvig and A. Das and U.
Tabori and M. Hasselblatt and A. Korshunov$^*$ and Z.
Abdullaev and M. Quezado and K. Aldape and P. Harter$^*$ and
M. Snuderl and J. Hench and S. Frank and T. Acker and S.
Brandner and F. Winkler$^*$ and P. Wesseling and S. M.
Pfister$^*$ and D. E. Reuss$^*$ and W. Wick$^*$ and A. von
Deimling$^*$ and D. T. W. Jones$^*$ and F. Sahm$^*$},
title = {{G}lioblastomas with primitive neuronal component harbor a
distinct methylation and copy-number profile with
inactivation of {TP}53, {PTEN}, and {RB}1.},
journal = {Acta neuropathologica},
volume = {142},
number = {1},
issn = {1432-0533},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2021-00909},
pages = {179-189},
year = {2021},
note = {#EA:B300#LA:B300# /2021 Jul;142(1):179-189},
abstract = {Glioblastoma IDH-wildtype presents with a wide histological
spectrum. Some features are so distinctive that they are
considered as separate histological variants or patterns for
the purpose of classification. However, these usually lack
defined (epi-)genetic alterations or profiles correlating
with this histology. Here, we describe a molecular subtype
with overlap to the unique histological pattern of
glioblastoma with primitive neuronal component. Our cohort
consists of 63 IDH-wildtype glioblastomas that harbor a
characteristic DNA methylation profile. Median age at
diagnosis was 59.5 years. Copy-number variations and
genetic sequencing revealed frequent alterations in TP53,
RB1 and PTEN, with fewer gains of chromosome 7 and
homozygous CDKN2A/B deletions than usually described for
IDH-wildtype glioblastoma. Gains of chromosome 1 were
detected in more than half of the cases. A poorly
differentiated phenotype with frequent absence of GFAP
expression, high proliferation index and strong staining for
p53 and TTF1 often caused misleading histological
classification as carcinoma metastasis or primitive
neuroectodermal tumor. Clinically, many patients presented
with leptomeningeal dissemination and spinal metastasis.
Outcome was poor with a median overall survival of only
12 months. Overall, we describe a new molecular subtype of
IDH-wildtype glioblastoma with a distinct histological
appearance and genetic signature.},
keywords = {Classification (Other) / DNA methylation (Other) / GBM
(Other) / PNET (Other) / Phenotype (Other) / Plasticity
(Other)},
cin = {B300 / HD01 / B062 / B360 / BE01 / B320},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)BE01-20160331 / I:(DE-He78)B320-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33876327},
doi = {10.1007/s00401-021-02302-6},
url = {https://inrepo02.dkfz.de/record/168435},
}