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@ARTICLE{Banan:157450,
author = {R. Banan and D. Stichel$^*$ and A. Bleck and B. Hong and U.
Lehmann and A. Suwala$^*$ and A. Reinhardt$^*$ and D.
Schrimpf$^*$ and R. Buslei and C. Stadelmann and K. Ehlert
and M. Prinz and T. Acker and J. Schittenhelm and D. Kaul
and L. Schweizer$^*$ and D. Capper$^*$ and P. Harter$^*$ and
N. Etminan and D. T. W. Jones$^*$ and S. M. Pfister$^*$ and
C. Herold-Mende and W. Wick$^*$ and F. Sahm$^*$ and A. von
Deimling$^*$ and C. Hartmann and D. Reuß$^*$},
title = {{I}nfratentorial {IDH}-mutant astrocytoma is a distinct
subtype.},
journal = {Acta neuropathologica},
volume = {140},
number = {4},
issn = {1432-0533},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2020-01629},
pages = {569-581},
year = {2020},
note = {2020 Oct;140(4):569-581#LA:B300#},
abstract = {Diffuse IDH-mutant astrocytic tumors are rarely diagnosed
in the cerebellum or brainstem. In this multi-institutional
study, we characterized a series of primary infratentorial
IDH-mutant astrocytic tumors with respect to clinical and
molecular parameters. We report that about $80\%$ of IDH
mutations in these tumors are of non-IDH1-R132H variants
which are rare in supratentorial astrocytomas. Most
frequently, IDH1-R132C/G and IDH2-R172S/G mutations were
present. Moreover, the frequencies of ATRX-loss and MGMT
promoter methylation, which are typically associated with
IDH mutations in supratentorial astrocytic tumors, were
significantly lower in the infratentorial compartment. Gene
panel sequencing revealed two samples with
IDH1-R132C/H3F3A-K27M co-mutations. Genome-wide DNA
methylation as well as chromosomal copy number profiling
provided further evidence for a molecular distinctiveness of
infratentorial IDH-mutant astrocytomas. Clinical outcome of
patients with infratentorial IDH-mutant astrocytomas is
significantly better than that of patients with diffuse
midline gliomas, H3K27M-mutant (p < 0.005) and
significantly worse than that of patients with
supratentorial IDH-mutant astrocytomas (p = 0.028). The
presented data highlight the very existence and
distinctiveness of infratentorial IDH-mutant astrocytomas
that have important implications for diagnostics and
prognostication. They imply that molecular testing is
critical for detection of these tumors, since many of these
tumors cannot be identified by immunohistochemistry applied
for the mutated IDH1-R132H protein or loss of ATRX.},
cin = {B300 / HD01 / BE01 / FM01 / B360 / B062 / B320},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)BE01-20160331 / I:(DE-He78)FM01-20160331 /
I:(DE-He78)B360-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)B320-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32776277},
doi = {10.1007/s00401-020-02194-y},
url = {https://inrepo02.dkfz.de/record/157450},
}