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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},
}