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@ARTICLE{Kbel:284647,
      author       = {M. Köbel and R. Z. Yang and E. Y. Kang and Z. Al-Shamma
                      and L. S. Cook and M. Kinloch and M. S. Carey and L. Hopkins
                      and G. S. Nelson and K. J. McManus and F. S. Vizeacoumar and
                      F. J. Vizeacoumar and A. Freywald and Y. Fu and D. E.
                      Reuss$^*$ and C.-H. Lee},
      title        = {{S}urvey of {NF}1 inactivation by surrogate
                      immunohistochemistry in ovarian carcinomas.},
      journal      = {Gynecologic oncology},
      volume       = {178},
      issn         = {0090-8258},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2023-02050},
      pages        = {80 - 88},
      year         = {2023},
      abstract     = {Inhibition of the MAPK pathway by MEK inhibitors (MEKi) is
                      currently a therapeutic standard in several cancer types,
                      including ovarian low-grade serous carcinoma (LGSC). A
                      common MAPK pathway alteration in tubo-ovarian high-grade
                      serous carcinoma (HGSC) is the genomic inactivation of
                      neurofibromin 1 (NF1). The primary objectives of our study
                      were to survey the prevalence of NF1 inactivation in the
                      principal ovarian carcinoma histotype as well as to evaluate
                      its associations with clinico-pathological parameters and
                      key biomarkers including BRCA1/2 status in HGSC.A recently
                      commercialized NF1 antibody (clone NFC) was orthogonally
                      validated on an automated immunohistochemistry (IHC)
                      platform and IHC was performed on tissue microarrays
                      containing 2140 ovarian carcinoma cases. Expression was
                      interpreted as loss/inactivated (complete or subclonal)
                      versus normal/retained.Loss of NF1 expression was detected
                      in 250/1429 $(17.4\%)$ HGSC including $11\%$ with subclonal
                      loss. Survival of NF1-inactivated HGSC patients was
                      intermediate between favorable BRCA1/2 mutated HGSC and
                      unfavorable CCNE1 high-level amplified HGSC. NF1
                      inactivation was mutually exclusive with CCNE1 high-level
                      amplifications, co-occurred with RB1 loss and occurred at
                      similar frequencies in BRCA1/2 mutated versus wild-type
                      HGSC. NF1 loss was found in 21/286 $(7.3\%)$ endometrioid
                      carcinomas with a favorable prognostic association (p =
                      0.048), and in 4/64 $(5.9\%)$ LGSC, mutually exclusive with
                      other driver events.NF1 inactivation occurs in a significant
                      subset of BRCA1/2 wild-type HGSC and a subset of LGSC. While
                      the functional effects of NF1 inactivation need to be
                      further characterized, this signifies a potential
                      therapeutic opportunity to explore targeting NF1
                      inactivation in these tumors.},
      keywords     = {High-grade serous carcinoma (Other) / NF1 (Other) / Ovarian
                      cancer (Other)},
      cin          = {B300 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B300-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37820398},
      doi          = {10.1016/j.ygyno.2023.09.016},
      url          = {https://inrepo02.dkfz.de/record/284647},
}