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@ARTICLE{Witt:182138,
      author       = {J. Witt$^*$ and S. Haupt and A. Ahadova$^*$ and L.
                      Bohaumilitzky$^*$ and V. Fuchs$^*$ and A. Ballhausen$^*$ and
                      M. J. Przybilla$^*$ and M. Jendrusch$^*$ and T. T. Seppälä
                      and D. Fürst and T. Walle and E. Busch and G. M. Haag$^*$
                      and R. Hüneburg and J. Nattermann and M. von Knebel
                      Doeberitz$^*$ and V. Heuveline and M. Kloor$^*$},
      title        = {{A} simple approach for detecting {HLA}-{A}*02 alleles in
                      archival formalin-fixed paraffin-embedded tissue samples and
                      an application example for studying cancer immunoediting.},
      journal      = {HLA},
      volume       = {101},
      number       = {1},
      issn         = {0001-2815},
      address      = {Oxford},
      publisher    = {Wiley},
      reportid     = {DKFZ-2022-02455},
      pages        = {24-33},
      year         = {2023},
      note         = {#EA:F210#LA:F210# / 2023 Jan;101(1):24-33},
      abstract     = {The human leukocyte antigen (HLA) system represents a
                      central component of the antigen presentation machinery. As
                      every patient possesses a defined set of HLA molecules, only
                      certain antigens can be presented on the cell surface. Thus,
                      studying HLA type-dependent antigen presentation can improve
                      the understanding of variation in susceptibility to various
                      diseases, including infectious diseases and cancer. In
                      archival formalin-fixed paraffin-embedded (FFPE) tissue, the
                      HLA type is difficult to analyze due to fragmentation of
                      DNA, hindering the application of commonly used assays that
                      rely on long DNA stretches. Addressing these difficulties,
                      we present a refined approach for characterizing presence or
                      absence of HLA-A*02, the most common HLA-A allele in the
                      Caucasian population, in archival samples. We validated our
                      genotyping strategy in a cohort of 90 samples with HLA
                      status obtained by an NGS-based method. $90\%$ (n=81) of the
                      samples could be analyzed with the approach. For all of
                      them, the presence or absence of HLA-A*02 alleles was
                      correctly determined with the method, demonstrating $100\%$
                      sensitivity and specificity $(95\%$ CI: 91.40 to $100\%$ and
                      91.19 to $100\%).$ Furthermore, we provide an example of
                      application in an independent cohort of 73 FFPE
                      microsatellite-unstable (MSI) colorectal cancer samples. As
                      MSI cancer cells encompass a high number of mutations in
                      coding microsatellites (cMS), leading to the generation of
                      highly immunogenic frameshift peptide (FSP) antigens, they
                      are ideally suited for studying relations between the
                      mutational landscape of tumor cells and interindividual
                      differences in the immune system, including the HLA
                      genotype. Overall, our method can help to promote studying
                      HLA type-dependency during the pathogenesis of a wide range
                      of diseases, making archival and historic tissue samples
                      accessible for identifying HLA-A*02 alleles. This article is
                      protected by copyright. All rights reserved.},
      keywords     = {Cancer immunoediting (Other) / Formalin-fixed
                      paraffin-embedded tissue samples (Other) / HLA typing
                      (Other) / MSI cancer (Other)},
      cin          = {F210 / D120},
      ddc          = {610},
      cid          = {I:(DE-He78)F210-20160331 / I:(DE-He78)D120-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36251018},
      doi          = {10.1111/tan.14846},
      url          = {https://inrepo02.dkfz.de/record/182138},
}