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@ARTICLE{WittigBlaich:120588,
author = {S. Wittig-Blaich$^*$ and R. Wittig$^*$ and S. Schmidt and
S. Lyer$^*$ and M. Bewerunge-Hudler$^*$ and S.
Gronert-Sum$^*$ and O. Strobel-Freidekind$^*$ and C. Müller
and M. List and A. Jaskot and H. Christiansen and M. Hafner
and D. Schadendorf$^*$ and I. Block and J. Mollenhauer},
title = {{S}ystematic screening of isogenic cancer cells identifies
{DUSP}6 as context-specific synthetic lethal target in
melanoma.},
journal = {OncoTarget},
volume = {8},
number = {14},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-01017},
pages = {23760-23774},
year = {2017},
abstract = {Next-generation sequencing has dramatically increased
genome-wide profiling options and conceptually initiates the
possibility for personalized cancer therapy.
State-of-the-art sequencing studies yield large candidate
gene sets comprising dozens or hundreds of mutated genes.
However, few technologies are available for the systematic
downstream evaluation of these results to identify novel
starting points of future cancer therapies.We improved and
extended a site-specific recombination-based system for
systematic analysis of the individual functions of a large
number of candidate genes. This was facilitated by a novel
system for the construction of isogenic constitutive and
inducible gain- and loss-of-function cell lines.
Additionally, we demonstrate the construction of isogenic
cell lines with combinations of the traits for advanced
functional in vitro analyses. In a proof-of-concept
experiment, a library of 108 isogenic melanoma cell lines
was constructed and 8 genes were identified that
significantly reduced viability in a discovery screen and in
an independent validation screen. Here, we demonstrate the
broad applicability of this recombination-based method and
we proved its potential to identify new drug targets via the
identification of the tumor suppressor DUSP6 as potential
synthetic lethal target in melanoma cell lines with BRAF
V600E mutations and high DUSP6 expression.},
cin = {B050 / W110 / L401},
ddc = {610},
cid = {I:(DE-He78)B050-20160331 / I:(DE-He78)W110-20160331 /
I:(DE-He78)L401-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28423600},
pmc = {pmc:PMC5410342},
doi = {10.18632/oncotarget.15863},
url = {https://inrepo02.dkfz.de/record/120588},
}