% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Lffler:129069,
      author       = {H. Löffler$^*$ and N. Pfarr and M. Kriegsmann and V.
                      Endris and T. Hielscher$^*$ and P. Lohneis and G. Folprecht
                      and A. Stenzinger and M. Dietel and W. Weichert$^*$ and A.
                      Krämer$^*$},
      title        = {{M}olecular driver alterations and their clinical relevance
                      in cancer of unknown primary site.},
      journal      = {OncoTarget},
      volume       = {7},
      number       = {28},
      issn         = {1949-2553},
      address      = {[S.l.]},
      publisher    = {Impact Journals LLC},
      reportid     = {DKFZ-2017-05074},
      pages        = {44322 - 44329},
      year         = {2016},
      abstract     = {Cancer of unknown primary (CUP) is defined as metastatic
                      solid malignancy where no primary tumor is detected despite
                      appropriate staging. About $90\%$ of CUP represent
                      adenocarcinoma or undifferentiated carcinoma. Since therapy
                      regimens are only modestly effective, identification of the
                      molecular landscape of these neoplasms might be a promising
                      approach to direct CUP therapy and aid in tumor
                      classification. We screened a cohort of 128 patients with
                      adenocarcinoma or undifferentiated carcinoma meeting the
                      definition of CUP. Massive parallel multigene sequencing of
                      50 genes, which had been selected due to their relevance as
                      oncogenic drivers or druggable molecular targets could
                      ultimately be performed on samples from 55 patients for whom
                      complete clinical datasets were also available. Overall, 60
                      tumor-specific mutations and 29 amplifications/deletions, as
                      revealed by coverage analysis, were detected in 46 cases
                      $(84\%).$ The most frequently mutated genes were TP53 (30
                      cases, $55\%),$ KRAS (9 cases, $16\%),$ CDKN2A (5 cases,
                      $9\%),$ and SMAD4 (5 cases, $9\%).$ The most frequently
                      deleted gene was CDKN2A (8 cases, $15\%).$ KRAS and CDKN2A
                      mutations significantly correlated with poor
                      progression-free survival (PFS) and, in case of KRAS,
                      overall survival (OS). WIldtype TP53 and female sex defined
                      a relatively favorable category, with favorable PFS and OS.
                      8 cases $(15\%)$ harbored mutations that may be targetable
                      by currently approved drugs. Taken together, Mutations of
                      relevant driver genes are present in the vast majority of
                      CUP tumors. Some of them impact on prognosis and a subset is
                      putatively druggable.},
      cin          = {G330 / C060 / L101 / L701 / L201 / L301},
      ddc          = {610},
      cid          = {I:(DE-He78)G330-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)L101-20160331 / I:(DE-He78)L701-20160331 /
                      I:(DE-He78)L201-20160331 / I:(DE-He78)L301-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27322425},
      pmc          = {pmc:PMC5190099},
      doi          = {10.18632/oncotarget.10035},
      url          = {https://inrepo02.dkfz.de/record/129069},
}