% 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{Staffa:127549,
      author       = {L. Staffa$^*$ and F. Echterdiek$^*$ and N. Nelius$^*$ and
                      A. Benner$^*$ and W. Werft$^*$ and B. Lahrmann and N. Grabe
                      and M. Schneider and M. Tariverdian and M. von Knebel
                      Doeberitz$^*$ and H. Bläker and M. Kloor$^*$},
      title        = {{M}ismatch repair-deficient crypt foci in {L}ynch
                      syndrome--molecular alterations and association with
                      clinical parameters.},
      journal      = {PLoS one},
      volume       = {10},
      number       = {3},
      issn         = {1932-6203},
      address      = {Lawrence, Kan.},
      publisher    = {PLoS},
      reportid     = {DKFZ-2017-03572},
      pages        = {e0121980 -},
      year         = {2015},
      abstract     = {Lynch syndrome is caused by germline mutations of DNA
                      mismatch repair (MMR) genes, most frequently MLH1 and MSH2.
                      Recently, MMR-deficient crypt foci (MMR-DCF) have been
                      identified as a novel lesion which occurs at high frequency
                      in the intestinal mucosa from Lynch syndrome mutation
                      carriers, but very rarely progress to cancer. To shed light
                      on molecular alterations and clinical associations of
                      MMR-DCF, we systematically searched the intestinal mucosa
                      from Lynch syndrome patients for MMR-DCF by
                      immunohistochemistry. The identified lesions were
                      characterised for alterations in microsatellite-bearing
                      genes with proven or suspected role in malignant
                      transformation. We demonstrate that the prevalence of
                      MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the
                      colorectum of Lynch syndrome patients) was significantly
                      associated with patients' age, but not with patients'
                      gender. No MMR-DCF were detectable in the mucosa of patients
                      with sporadic MSI-H colorectal cancer (n = 12).
                      Microsatellite instability of at least one tested marker was
                      detected in $89\%$ of the MMR-DCF examined, indicating an
                      immediate onset of microsatellite instability after MMR gene
                      inactivation. Coding microsatellite mutations were most
                      frequent in the genes HT001 (ASTE1) with $33\%,$ followed by
                      AIM2 $(17\%)$ and BAX $(10\%).$ Though MMR deficiency alone
                      appears to be insufficient for malignant transformation, it
                      leads to measurable microsatellite instability even in
                      single MMR-deficient crypts. Our data indicate for the first
                      time that the frequency of MMR-DCF increases with patients'
                      age. Similar patterns of coding microsatellite instability
                      in MMR-DCF and MMR-deficient cancers suggest that certain
                      combinations of coding microsatellite mutations, including
                      mutations of the HT001, AIM2 and BAX gene, may contribute to
                      the progression of MMR-deficient lesions into MMR-deficient
                      cancers.},
      keywords     = {AIM2 protein, human (NLM Chemicals) / ASTE1 protein, human
                      (NLM Chemicals) / Adaptor Proteins, Signal Transducing (NLM
                      Chemicals) / BAX protein, human (NLM Chemicals) /
                      DNA-Binding Proteins (NLM Chemicals) / MLH1 protein, human
                      (NLM Chemicals) / Nuclear Proteins (NLM Chemicals) /
                      Proteins (NLM Chemicals) / bcl-2-Associated X Protein (NLM
                      Chemicals) / MSH2 protein, human (NLM Chemicals) / MutL
                      Protein Homolog 1 (NLM Chemicals) / MutS Homolog 2 Protein
                      (NLM Chemicals)},
      cin          = {C060 / G105},
      ddc          = {500},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)G105-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25816162},
      pmc          = {pmc:PMC4376900},
      doi          = {10.1371/journal.pone.0121980},
      url          = {https://inrepo02.dkfz.de/record/127549},
}