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@ARTICLE{Patel:300147,
author = {A. J. Patel$^*$ and K. Göbel$^*$ and S. Ille and F.
Hinz$^*$ and N. Schoebe$^*$ and H. Bogumil$^*$ and J.
Meyer$^*$ and M. Brehm$^*$ and H. Kardo$^*$ and D.
Schrimpf$^*$ and A. Lomakin$^*$ and M. Ritter$^*$ and P.
Göller$^*$ and P. Kerbs$^*$ and L. Pfeifer$^*$ and S.
Hamelmann$^*$ and C. Blume$^*$ and F. Ippen$^*$ and N.
Berghaus$^*$ and P. Euskirchen$^*$ and L. Schweizer$^*$ and
C. Hultschig and N. Van Roy and J. Van Dorpe and J. Van der
Meulen and S. Loontiens and F. Dedeurwaerdere and H. Leske
and S. Halldórsson and G. Fox and S. Deacon and I. Cahyani
and N. Holmes and S. Wibowo and R. Munro and D. Martin and
A. Sharif and M. Housley and R. Goldspring and S. Brandner
and S. Roy and J. Hench and S. Frank and A. Unterberg and V.
Goidts$^*$ and N. Jäger$^*$ and S. Paine and S. Smith and
C. Herold-Mende and W. Wick$^*$ and S. Pfister$^*$ and E. O.
Vik-Mo and A. von Deimling$^*$ and S. Krieg and D. T.
Jones$^*$ and M. Loose and M. Schlesner and M. Sill$^*$ and
F. Sahm$^*$},
title = {{P}rospective, multicenter validation of a platform for
rapid molecular profiling of central nervous system tumors.},
journal = {Nature medicine},
volume = {31},
number = {5},
issn = {1078-8956},
address = {[New York, NY]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-00638},
pages = {1567-1577},
year = {2025},
note = {#EA:B300#LA:B300#LA:B062# / 2025 May;31(5):1567-1577},
abstract = {Molecular data integration plays a central role in central
nervous system (CNS) tumor diagnostics but currently used
assays pose limitations due to technical complexity,
equipment and reagent costs, as well as lengthy turnaround
times. We previously reported the development of Rapid-CNS2,
an adaptive-sampling-based nanopore sequencing workflow.
Here we comprehensively validated and further developed
Rapid-CNS2 for intraoperative use. It now offers real-time
methylation classification and DNA copy number information
within a 30-min intraoperative window, followed by
comprehensive molecular profiling within 24 h, covering the
complete spectrum of diagnostically and therapeutically
relevant information for the respective entity. We validated
Rapid-CNS2 in a multicenter setting on 301 archival and
prospective samples including 18 samples sequenced
intraoperatively. To broaden the utility of
methylation-based CNS tumor classification, we developed
MNP-Flex, a platform-agnostic methylation classifier
encompassing 184 classes. MNP-Flex achieved $99.6\%$
accuracy for methylation families and $99.2\%$ accuracy for
methylation classes with clinically applicable thresholds
across a global validation cohort of more than 78,000 frozen
and formalin-fixed paraffin-embedded samples spanning five
different technologies. Integration of these tools has the
potential to advance CNS tumor diagnostics by providing
broad access to rapid, actionable molecular insights crucial
for personalized treatment strategies.},
cin = {B300 / HD01 / B450 / BE01 / FM01 / B067 / B062 / B320 /
B360},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B450-20160331 / I:(DE-He78)BE01-20160331 /
I:(DE-He78)FM01-20160331 / I:(DE-He78)B067-20160331 /
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:40133526},
doi = {10.1038/s41591-025-03562-5},
url = {https://inrepo02.dkfz.de/record/300147},
}