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@ARTICLE{Hardin:275480,
author = {E. C. Hardin$^*$ and S. Schmid and A. Sommerkamp$^*$ and C.
Bodden$^*$ and A.-E. Heipertz$^*$ and P. Sievers$^*$ and A.
Wittmann$^*$ and T. Milde$^*$ and S. Pfister$^*$ and A. von
Deimling$^*$ and S. Horn and N. A. Herz and M. Simon and A.
A. Perera$^*$ and A. Azizi and O. Cruz and S. Curry and A.
Van Damme and M. Garami and D. Hargrave and A. Kattamis and
B. F. Kotnik and P. Lähteenmäki and K. Scheinemann and A.
Y. N. Schouten-van Meeteren and A. Sehested and E. Viscardi
and O. M. Wormdal and M. Zapotocky and D. S. Ziegler and A.
Koch and P. H. Driever and O. Witt$^*$ and D. Capper$^*$ and
F. Sahm$^*$ and D. Jones$^*$ and C. M. van Tilburg$^*$},
title = {{LOGGIC} {C}ore {B}io{C}linical {D}ata {B}ank: {A}dded
clinical value of {RNA}-{S}eq in an international molecular
diagnostic registry for pediatric low-grade glioma
patients.},
journal = {Neuro-Oncology},
volume = {25},
number = {11},
issn = {1522-8517},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2023-00787},
pages = {2087-2097},
year = {2023},
note = {#EA:B310#LA:B310# / 2023 Nov 2;25(11):2087-2097},
abstract = {The international, multicenter registry LOGGIC Core
BioClinical Data Bank aims to enhance the understanding of
tumor biology in pediatric low-grade glioma (pLGG) and
provide clinical and molecular data to support treatment
decisions and interventional trial participation. Hence, the
question arises whether implementation of RNA sequencing
(RNA-Seq) using Fresh Frozen (FrFr) tumor tissue in addition
to gene panel and DNA methylation analysis improves
diagnostic accuracy and provides additional clinical
benefit.Analysis of patients age 0 to 21 years, enrolled in
Germany between 04/2019 and 02/2021, and for whom FrFr
tissue was available. Central reference histopathology,
immunohistochemistry, 850k DNA methylation analysis, gene
panel sequencing and RNA-Seq were performed.FrFr tissue was
available in 178/379 enrolled cases. RNA-Seq was performed
on 125 of these samples. We confirmed KIAA1549::BRAF-fusion
(n=71), BRAF V600E-mutation (n=12) and alterations in FGFR1
(n=14) as the most frequent alterations, among other common
molecular drivers (n=12). . N=16 cases $(13\%)$ presented
rare gene fusions (e.g. TPM3::NTRK1, EWSR1::VGLL1,
SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n=27 cases
$(22\%),$ RNA-Seq detected a driver alteration not otherwise
identified (22/27 actionable). The rate of driver alteration
detection was hereby increased from $75\%$ to $97\%.$
Furthermore, FGFR1 ITD (n=6) were only detected by RNA-Seq
using current bioinformatics pipelines, leading to a change
in analysis protocols.The addition of RNA-Seq to current
diagnostic methods improves diagnostic accuracy, making
precision oncology treatments
(MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible. We
propose to include RNA-Seq as part of routine diagnostics
for all pLGG patients, especially when no common pLGG
alteration was identified.},
keywords = {RNA sequencing (Other) / actionable drivers (Other) /
molecular profiling (Other) / pLGG (Other) / rare gene
fusions (Other)},
cin = {B310 / HD01 / B300 / B360 / BE01 / B062},
ddc = {610},
cid = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B300-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)BE01-20160331 / I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37075810},
doi = {10.1093/neuonc/noad078},
url = {https://inrepo02.dkfz.de/record/275480},
}