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@ARTICLE{Menzel:284931,
      author       = {M. Menzel and S. Ossowski and S. Kral and P. Metzger and P.
                      Horak$^*$ and R. Marienfeld and M. Börries$^*$ and S.
                      Wolter and M. Ball and O. Neumann and S. Armeanu-Ebinger and
                      C. Schroeder and U. Matysiak and H. Goldschmid and V.
                      Schipperges and A. Fürstberger and M. Allgäuer and T.
                      Eberhardt and J. Niewöhner and A. Blaumeiser$^*$ and C.
                      Ploeger and T. B. Haack and T. K. Y. Tay and O. Kelemen and
                      T. Pauli and M. Kirchner and K. Kluck and A. Ott and M.
                      Renner$^*$ and J. Admard and A. Gschwind and S. Lassmann and
                      H. Kestler and F. Fend and A. L. Illert$^*$ and M. Werner
                      and P. Möller and T. T. W. Seufferlein and N. Malek and P.
                      Schirmacher$^*$ and S. Fröhling$^*$ and D. Kazdal and J.
                      Budczies$^*$ and A. Stenzinger$^*$},
      title        = {{M}ulticentric pilot study to standardize clinical whole
                      exome sequencing ({WES}) for cancer patients.},
      journal      = {npj precision oncology},
      volume       = {7},
      number       = {1},
      issn         = {2397-768X},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2023-02131},
      pages        = {106},
      year         = {2023},
      note         = {#EA:B340#},
      abstract     = {A growing number of druggable targets and national
                      initiatives for precision oncology necessitate broad genomic
                      profiling for many cancer patients. Whole exome sequencing
                      (WES) offers unbiased analysis of the entire coding
                      sequence, segmentation-based detection of copy number
                      alterations (CNAs), and accurate determination of complex
                      biomarkers including tumor mutational burden (TMB),
                      homologous recombination repair deficiency (HRD), and
                      microsatellite instability (MSI). To assess the
                      inter-institution variability of clinical WES, we performed
                      a comparative pilot study between German Centers of
                      Personalized Medicine (ZPMs) from five participating
                      institutions. Tumor and matched normal DNA from 30 patients
                      were analyzed using custom sequencing protocols and
                      bioinformatic pipelines. Calling of somatic variants was
                      highly concordant with a positive percentage agreement (PPA)
                      between 91 and $95\%$ and a positive predictive value (PPV)
                      between 82 and $95\%$ compared with a three-institution
                      consensus and full agreement for 16 of 17 druggable targets.
                      Explanations for deviations included low VAF or coverage,
                      differing annotations, and different filter protocols. CNAs
                      showed overall agreement in $76\%$ for the genomic sequence
                      with high wet-lab variability. Complex biomarkers correlated
                      strongly between institutions (HRD: 0.79-1, TMB: 0.97-0.99)
                      and all institutions agreed on microsatellite instability.
                      This study will contribute to the development of quality
                      control frameworks for comprehensive genomic profiling and
                      sheds light onto parameters that require stringent
                      standardization.},
      cin          = {B340 / HD01 / FR01 / MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)B340-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)FR01-20160331 / I:(DE-He78)MU01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37864096},
      pmc          = {pmc:PMC10589320},
      doi          = {10.1038/s41698-023-00457-x},
      url          = {https://inrepo02.dkfz.de/record/284931},
}