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@ARTICLE{Reuss:285695,
author = {D. E. Reuss$^*$ and D. Schrimpf$^*$ and D. Stichel$^*$ and
A. Ebrahimi and C. Dampier and K. Aldape and M. Snuderl and
D. Capper$^*$ and M. Sill$^*$ and D. T. W. Jones$^*$ and S.
M. Pfister$^*$ and F. Sahm$^*$ and A. von Deimling$^*$},
title = {{R}eference on copy number variations in pleomorphic
xanthoastrocytoma: {I}mplications for diagnostic approach.},
journal = {Free Neuropathology},
volume = {4},
issn = {2699-4445},
address = {Muenster},
publisher = {Prof. Dr. Werner Paulus, University of Muenster, Institute
of Neuropathology},
reportid = {DKFZ-2023-02510},
pages = {4-19},
year = {2023},
note = {#EA:B300#LA:B300#},
abstract = {Pleomorphic xanthoastrocytoma (PXA) poses a diagnostic
challenge. The present study relies on methylation-based
predictions and focuses on copy number variations (CNV) in
PXA. We identified 551 tumors from patients having received
the histologic diagnosis or differential diagnosis
pleomorphic xanthoastrocytoma (PXA) uploaded to the web page
www.molecularneuropathology.org. Of these 551 tumors, 165
received the prediction 'methylation class (anaplastic)
pleomorphic xanthoastrocytoma' with a calibrated score >=0.9
by the brain tumor classifier version v12.8 and, therefore,
were defined the PXA reference set designated mcPXAref. In
addition to these 165 mcPXAref, 767 other tumors received
the prediction mcPXA with a calibrated score >=0.9 but
without a histological PXA diagnosis. The total number of
individual tumors predicted by histology and/or by methylome
based classification as PXA, mcPXA or both was 1318, and
these were designated the study cohort. The selection of a
control cohort was guided by methylation-based predictions
recurrently observed for the other 386/551 tumors diagnosed
as histologic PXA. 131/386 received predictions for another
entity besides PXA with a score >=0.9. Control tumors
corresponding to the 11 most common other predictions were
selected, adding up to 1100 reference cases. CNV profiles
were calculated from all methylation datasets of the study
and control cohorts. Special attention was given to the 7/10
signature, gene amplifications and homozygous deletion of
CDKN2A/B. Comparison of CNV in the subsets of the study
cohort and the control cohort were used to establish
relations independent of histological diagnoses. Tumors in
mcPXA were highly homogenous in regard to CNV alterations,
irrespective of the histological diagnoses. The 7/10
signature commonly present in glioblastoma, IDH-wildtype,
was present in $15-20\%$ of mcPXA, whereas amplification of
oncogenes (likewise common in glioblastoma) was very rare in
mcPXA $(<1\%).$ In contrast, the histology-based PXA group
exhibited high variance in regard to methylation classes as
well as to CNVs. Our data add to the notion, that
histologically defined PXA likely only represent a subset of
the biological disease.},
keywords = {7/10 signature (Other) / Amplification (Other) / CDKN2A/B
(Other) / CNV (Other) / Classification (Other) / Copy Number
Variations (Other) / EGFR (Other) / Homozygous deletion
(Other) / Methylation (Other) / PXA (Other) / Pleomorphic
Xanthoastrocytoma (Other)},
cin = {B300 / HD01 / BE01 / B062 / B360},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)BE01-20160331 / 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:38026572},
pmc = {pmc:PMC10646999},
doi = {10.17879/FREENEUROPATHOLOGY-2023-5156},
url = {https://inrepo02.dkfz.de/record/285695},
}