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@ARTICLE{Pfarr:120541,
      author       = {N. Pfarr and R. Penzel and V. Endris and C. Lier and C.
                      Flechtenmacher and A.-L. Volckmar and M. Kirchner$^*$ and J.
                      Budczies and J. Leichsenring and E. Herpel and A. Noske and
                      W. Weichert$^*$ and A. Schneeweiss$^*$ and P.
                      Schirmacher$^*$ and H.-P. Sinn and A. Stenzinger},
      title        = {{T}argeted next-generation sequencing enables reliable
                      detection of {HER}2 ({ERBB}2) status in breast cancer and
                      provides ancillary information of clinical relevance.},
      journal      = {Genes, chromosomes $\&$ cancer},
      volume       = {56},
      number       = {4},
      issn         = {1045-2257},
      address      = {New York, NY},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-00970},
      pages        = {255 - 265},
      year         = {2017},
      abstract     = {HER2-positive breast cancers are a heterogeneous group of
                      tumors, which share amplification and overexpression of
                      HER2. In routine diagnostics, the HER2 (ERBB2) status is
                      currently assessed by immunohistochemistry (IHC) and in situ
                      hybridization (ISH). Data on targeted next-generation
                      sequencing (NGS) approaches that could be used to determine
                      the HER2 status are sparse. Employing two breast
                      cancer-related gene panels, we performed targeted NGS of 41
                      FFPE breast cancers for which full pathological work-up
                      including ISH and IHC results was available. Selected cases
                      were analyzed by qPCR. Of the 41 cases, the HER2 status of
                      the 4 HER2-positive and 6 HER2-negative tumors was
                      independently detected by our NGS approach achieving a
                      concordance rate of $100\%.$ The remaining 31 cases were
                      equivocal HER2 cases by IHC of which 5 showed amplification
                      of HER2 by ISH. Our NGS approach classified all
                      non-amplified cases correctly as HER2 negative and
                      corroborated all but one of the 5 cases with amplified HER2
                      as detected by ISH. For the overall cohort, concordance
                      between the gold standard and NGS was $97.6\%$ (sensitivity
                      $88.9\%$ and specificity $100\%).$ Additionally, we observed
                      mutations in PIK3CA $(44\%),$ HER2 $(8\%),$ and CDH1 $(6\%)$
                      among others. Amplifications were found in CCND1 $(12\%),$
                      followed by MYC $(10\%)$ and EGFR $(2\%)$ and deletions in
                      CDKN2A $(10\%),$ MAP2K4 and PIK3R1 $(2\%$ each). We here
                      show that targeted NGS data can be used to interrogate the
                      HER2 status with high specificity and high concordance with
                      gold standard methods. Moreover, this approach identifies
                      additional genetic events that may be clinically
                      exploitable. © 2016 Wiley Periodicals, Inc.},
      cin          = {L701 / G825 / V964 / L101},
      ddc          = {570},
      cid          = {I:(DE-He78)L701-20160331 / I:(DE-He78)G825-20160331 /
                      I:(DE-He78)V964-20160331 / 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:27792260},
      doi          = {10.1002/gcc.22431},
      url          = {https://inrepo02.dkfz.de/record/120541},
}