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@ARTICLE{Stichel:166489,
author = {D. Stichel$^*$ and D. Schrimpf$^*$ and P. Sievers$^*$ and
A. Reinhardt$^*$ and A. K. Suwala$^*$ and M. Sill$^*$ and D.
E. Reuss$^*$ and A. Korshunov$^*$ and B. M. Casalini$^*$ and
A. C. Sommerkamp$^*$ and J. Ecker$^*$ and F. Selt$^*$ and D.
Sturm$^*$ and A. Gnekow and A. Koch and M. Simon and P.
Hernáiz Driever and U. Schüller and D. Capper$^*$ and C.
M. van Tilburg$^*$ and O. Witt$^*$ and T. Milde$^*$ and S.
M. Pfister$^*$ and D. T. W. Jones$^*$ and A. von
Deimling$^*$ and F. Sahm$^*$ and A. Wefers$^*$},
title = {{A}ccurate calling of {KIAA}1549-{BRAF} fusions from {DNA}
of human brain tumours using methylation array-based copy
number and gene panel sequencing data.},
journal = {Neuropathology $\&$ applied neurobiology},
volume = {47},
number = {3},
issn = {1365-2990},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2020-02932},
pages = {406-414},
year = {2021},
note = {#EA:B300#LA:B300#2021 Apr;47(3):406-414},
abstract = {KIAA1549-BRAF fusions occur in certain brain tumours and
provide druggable targets due to a constitutive activation
of the MAP-kinase pathway. We introduce workflows for
calling the KIAA1549-BRAF fusion from DNA
methylation-array-derived copy number as well as DNA panel
sequencing data.Copy number profiles were analysed by
automated screening and visual verification of a tandem
duplication on chromosome 7q34, indicative of the
KIAA1549-BRAF fusion. Pilocytic astrocytomas of the ICGC
cohort with known fusion status were used for validation.
KIAA1549-BRAF fusions were called from DNA panel sequencing
data using the fusion callers Manta, Arriba with modified
filtering criteria and deFuse. We screened DNA methylation
and panel sequencing data of 7790 specimens from brain
tumour and sarcoma entities.We identified the fusion in 337
brain tumours with both DNA methylation and panel sequencing
data. Among these, we detected the fusion from copy number
data in $84\%$ and from DNA panel sequencing data in more
than $90\%$ using Arriba with modified filters. While in
$74\%$ the KIAA1549-BRAF fusion was detected from both
methylation-array-derived copy number and panel sequencing
data, in $9\%$ it was detected from copy number data only
and in $16\%$ from panel data only. The fusion was almost
exclusively found in pilocytic astrocytomas, diffuse
leptomeningeal glioneuronal tumours and high-grade
astrocytomas with piloid features.The KIAA1549-BRAF fusion
can be reliably detected from either DNA methylation array
or DNA panel data. The use of both methods is recommended
for the most sensitive detection of this diagnostically and
therapeutically important marker.},
keywords = {KIAA1549-BRAF (Other) / Arriba (Other) / DNA methylation
(Other) / DNA panel sequencing (Other) / gene fusion (Other)
/ pilocytic astrocytoma (Other)},
cin = {B300 / B062 / HD01 / B360 / B310 / BE01},
ddc = {610},
cid = {I:(DE-He78)B300-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)B310-20160331 / I:(DE-He78)BE01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33336421},
doi = {10.1111/nan.12683},
url = {https://inrepo02.dkfz.de/record/166489},
}