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@ARTICLE{Sahm:130463,
      author       = {F. Sahm$^*$ and D. Schrimpf$^*$ and D. Jones$^*$ and J.
                      Meyer$^*$ and A. Kratz$^*$ and D. Reuss$^*$ and D.
                      Capper$^*$ and C. Koelsche$^*$ and A. Korshunov$^*$ and B.
                      P. O. Wiestler$^*$ and I. Buchhalter$^*$ and T. Milde$^*$
                      and F. Selt$^*$ and D. Sturm$^*$ and M. Kool$^*$ and M.
                      Hummel$^*$ and M. Bewerunge-Hudler$^*$ and C. Mawrin and U.
                      Schüller and C. Jungk and A. Wick and O. Witt$^*$ and M.
                      Platten$^*$ and C. Herold-Mende and A. Unterberg and S.
                      Pfister$^*$ and W. Wick$^*$ and A. von Deimling$^*$},
      title        = {{N}ext-generation sequencing in routine brain tumor
                      diagnostics enables an integrated diagnosis and identifies
                      actionable targets.},
      journal      = {Acta neuropathologica},
      volume       = {131},
      number       = {6},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-05542},
      pages        = {903 - 910},
      year         = {2016},
      abstract     = {With the number of prognostic and predictive genetic
                      markers in neuro-oncology steadily growing, the need for
                      comprehensive molecular analysis of neuropathology samples
                      has vastly increased. We therefore developed a customized
                      enrichment/hybrid-capture-based next-generation sequencing
                      (NGS) gene panel comprising the entire coding and selected
                      intronic and promoter regions of 130 genes recurrently
                      altered in brain tumors, allowing for the detection of
                      single nucleotide variations, fusions, and copy number
                      aberrations. Optimization of probe design, library
                      generation and sequencing conditions on 150 samples resulted
                      in a 5-workday routine workflow from the formalin-fixed
                      paraffin-embedded sample to neuropathological report. This
                      protocol was applied to 79 retrospective cases with
                      established molecular aberrations for validation and 71
                      prospective cases for discovery of potential therapeutic
                      targets. Concordance of NGS compared to established, single
                      biomarker methods was $98.0 \%,$ with discrepancies
                      resulting from one case where a TERT promoter mutation was
                      not called by NGS and three ATRX mutations not being
                      detected by Sanger sequencing. Importantly, in samples with
                      low tumor cell content, NGS was able to identify mutant
                      alleles that were not detectable by traditional methods.
                      Information derived from NGS data identified potential
                      targets for experimental therapy in 37/47 $(79 \%)$
                      glioblastomas, 9/10 $(90 \%)$ pilocytic astrocytomas, and
                      5/14 $(36 \%)$ medulloblastomas in the prospective target
                      discovery cohort. In conclusion, we present the settings for
                      high-throughput, adaptive next-generation sequencing in
                      routine neuropathology diagnostics. Such an approach will
                      likely become highly valuable in the near future for
                      treatment decision making, as more therapeutic targets
                      emerge and genetic information enters the classification of
                      brain tumors.},
      cin          = {G340 / G380 / B062 / G370 / G200 / C060 / W110 / G160 /
                      L101},
      ddc          = {610},
      cid          = {I:(DE-He78)G340-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)G370-20160331 /
                      I:(DE-He78)G200-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)W110-20160331 / I:(DE-He78)G160-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26671409},
      doi          = {10.1007/s00401-015-1519-8},
      url          = {https://inrepo02.dkfz.de/record/130463},
}