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@ARTICLE{BajwaTenBroeke:169971,
      author       = {S. W. Bajwa-Ten Broeke and A. Ballhausen$^*$ and A.
                      Ahadova$^*$ and M. Suerink and L. Bohaumilitzky$^*$ and F.
                      Seidler$^*$ and H. Morreau and T. van Wezel and J.
                      Krzykalla$^*$ and A. Benner$^*$ and N. F. de Miranda and M.
                      von Knebel Doeberitz$^*$ and M. Nielsen and M. Kloor$^*$},
      title        = {{T}he coding microsatellite mutation profile of
                      {PMS}2-deficient colorectal cancer.},
      journal      = {Experimental and molecular pathology},
      volume       = {122},
      issn         = {0014-4800},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2021-01671},
      pages        = {104668},
      year         = {2021},
      note         = {#LA:F210# / 2021 Oct;122:104668},
      abstract     = {Lynch syndrome (LS) is caused by a pathogenic heterozygous
                      germline variant in one of the DNA mismatch repair (MMR)
                      genes: MLH1, MSH2, MSH6 or PMS2. LS-associated colorectal
                      carcinomas (CRCs) are characterized by MMR deficiency and by
                      accumulation of multiple insertions/deletions at coding
                      microsatellites (cMS). MMR deficiency-induced variants at
                      defined cMS loci have a driver function and promote
                      tumorigenesis. Notably, PMS2 variant carriers face only a
                      slightly increased risk of developing CRC. Here, we
                      investigate whether this lower penetrance is also reflected
                      by differences in molecular features and cMS variant
                      patterns. Tumor DNA was extracted from formalin-fixed
                      paraffin-embedded (FFPE) tissue cores or sections (n = 90).
                      Tumors originated from genetically proven germline
                      pathogenic MMR variant carriers (including 14 PMS2-deficient
                      tumors). The mutational spectrum was analyzed using
                      fluorescently labeled primers specific for 18 cMS previously
                      described as mutational targets in MMR-deficient tumors.
                      Immune cell infiltration was analyzed by immunohistochemical
                      detection of T-cells on FFPE tissue sections. The cMS
                      spectrum of PMS2-deficient CRCs did not show any significant
                      differences from MLH1/MSH2-deficient CRCs. PMS2-deficient
                      tumors, however, displayed lower CD3-positive T-cell
                      infiltration compared to other MMR-deficient cancers (28.00
                      vs. 55.00 per 0.1 mm2, p = 0.0025). Our study demonstrates
                      that the spectrum of potentially immunogenic cMS variants in
                      CRCs from PMS2 gene variant carriers is similar to that
                      observed in CRCs from other MMR gene variant carriers. Lower
                      immune cell infiltration observed in PMS2-deficient CRCs
                      could be the result of alternative mechanisms of immune
                      evasion or immune cell exclusion, similar to those seen in
                      MMR-proficient tumors.},
      keywords     = {HNPCC (Other) / Hereditary colorectal cancer (Other) /
                      Immunology of cancer (Other) / Molecular pathways (Other)},
      cin          = {F210 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)F210-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34302852},
      doi          = {10.1016/j.yexmp.2021.104668},
      url          = {https://inrepo02.dkfz.de/record/169971},
}