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@ARTICLE{Mata:165857,
author = {D. A. Mata and J. K. Benhamida and A. L. Lin and C. M.
Vanderbilt and S.-R. Yang and L. B. Villafania and D. C.
Ferguson and P. Jonsson and A. M. Miller and V. Tabar and C.
W. Brennan and N. S. Moss and M. Sill$^*$ and R. Benayed and
I. K. Mellinghoff and M. K. Rosenblum and M. E. Arcila and
M. Ladanyi and T. A. Bale},
title = {{G}enetic and epigenetic landscape of {IDH}-wildtype
glioblastomas with {FGFR}3-{TACC}3 fusions.},
journal = {Acta Neuropathologica Communications},
volume = {8},
number = {1},
issn = {2051-5960},
address = {London},
publisher = {Biomed Central},
reportid = {DKFZ-2020-02433},
pages = {186},
year = {2020},
abstract = {A subset of glioblastomas (GBMs) harbors potentially
druggable oncogenic FGFR3-TACC3 (F3T3) fusions. However,
their associated molecular and clinical features are poorly
understood. Here we analyze the frequency of F3T3-fusion
positivity, its associated genetic and methylation profiles,
and its impact on survival in 906 IDH-wildtype GBM patients.
We establish an F3T3 prevalence of $4.1\%$ and delineate its
associations with cancer signaling pathway alterations.
F3T3-positive GBMs had lower tumor mutational and
copy-number alteration burdens than F3T3-wildtype GBMs.
Although F3T3 fusions were predominantly mutually exclusive
with other oncogenic RTK pathway alterations, they did
rarely co-occur with EGFR amplification. They were less
likely to harbor TP53 alterations. By methylation profiling,
they were more likely to be assigned the mesenchymal or RTK
II subclass. Despite being older at diagnosis and having
similar frequencies of MGMT promoter hypermethylation,
patients with F3T3-positive GBMs lived about 8 months
longer than those with F3T3-wildtype tumors. While
consistent with IDH-wildtype GBM, F3T3-positive GBMs exhibit
distinct biological features, underscoring the importance of
pursuing molecular studies prior to clinical trial
enrollment and targeted treatment.},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33168106},
doi = {10.1186/s40478-020-01058-6},
url = {https://inrepo02.dkfz.de/record/165857},
}