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@ARTICLE{Jurmeister:147359,
      author       = {P. Jurmeister$^*$ and C. Vollbrecht and A. Behnke and N.
                      Frost and A. Arnold and D. Treue and J.-C. Rückert and J.
                      Neudecker and L. Schweizer$^*$ and F. Klauschen and D. Horst
                      and M. Hummel and M. Dietel and M. von Laffert$^*$},
      title        = {{N}ext generation sequencing of lung adenocarcinoma
                      subtypes with intestinal differentiation reveals distinct
                      molecular signatures associated with histomorphology and
                      therapeutic options.},
      journal      = {Lung cancer},
      volume       = {138},
      issn         = {0169-5002},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2019-02480},
      pages        = {43 - 51},
      year         = {2019},
      note         = {EAL201LAL201},
      abstract     = {We aim to provide a better understanding of the molecular
                      landscape of primary lung adenocarcinomas with intestinal
                      differentiation.Five invasive mucinous adenocarcinomas (IMA)
                      and seven pulmonary enteric adenocarcinomas (PEAD) were
                      included in this study. Furthermore, we analyzed six
                      pulmonary colloid adenocarcinomas (CAD), including one
                      primary tumor, one metastasis, and two sample pairs
                      consisting of the primary colloid lung tumor and a matching
                      metastasis and an acinar component, respectively. All
                      samples were characterized using immunohistochemistry
                      (TTF-1, CK7, CK20, CDX2, Ki-67, ALK and PD-L1) and a next
                      generation sequencing panel covering 404 cancer-related
                      genes (FoundationOne® gene panel).While Ki-67 expression
                      was comparably low in IMA (range: $8-15\%)$ and in primary
                      CAD (range: $5-8\%),$ we observed considerably higher
                      proliferation rates in the non-colloid tumor compartment
                      $(16\%)$ and metastases $(72\%)$ from CAD, as well as in the
                      PEAD-group $(36-71\%).$ The overall tumor mutational burden
                      was lowest in IMA (2.5 mutations per megabase), intermediate
                      in CAD (5.8 mutations per megabase) and highest in PEAD
                      (16.8 mutations per megabase). KRAS mutations were frequent
                      in all three tumor subtypes, but TP53 mutations were mostly
                      limited to PEAD. While chromosomal alterations were rare in
                      IMA, we discovered MYC amplifications in three of four CAD.
                      Comparing primary and metastatic CAD, we observed the
                      acquisition of multiple mutations and chromosomal
                      alterations. PEAD had a variety of chromosomal alterations,
                      including two cases with RICTOR amplification. PD-L1
                      expression $(20\%,$ $50\%$ and $80\%$ of tumor cells) was
                      limited to three PEAD samples, only. In conclusion, we
                      provide a detailed insight into the molecular alterations
                      across and within the different subtypes of pulmonary
                      adenocarcinomas with intestinal differentiation. From a
                      clinical perspective, we provide data on potential treatment
                      strategies for patients with PEAD, including immunotherapy.},
      cin          = {L201},
      ddc          = {610},
      cid          = {I:(DE-He78)L201-20160331},
      pnm          = {899 - ohne Topic (POF3-899)},
      pid          = {G:(DE-HGF)POF3-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31634654},
      doi          = {10.1016/j.lungcan.2019.10.005},
      url          = {https://inrepo02.dkfz.de/record/147359},
}