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@ARTICLE{Weijers:286670,
      author       = {D. D. Weijers and S. Hirsch$^*$ and J. J. Bakhuizen and N.
                      van Engelen and L. A. Kester and M. E. G. Kranendonk and L.
                      S. Hiemcke-Jiwa and E. de Vos-Kerkhof and J. L. C. Loeffen
                      and R. Autry$^*$ and K. Pajtler$^*$ and N. Jäger$^*$ and M.
                      C. J. Jongmans and R. P. Kuiper},
      title        = {{M}olecular analysis of cancer genomes in children with
                      {L}ynch syndrome: {E}xploring causal associations.},
      journal      = {International journal of cancer},
      volume       = {154},
      number       = {8},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2024-00034},
      pages        = {1455-1463},
      year         = {2024},
      note         = {2024 Apr 15;154(8):1455-1463},
      abstract     = {Lynch syndrome (LS) predisposes to cancer in adulthood and
                      is caused by heterozygous germline variants in a mismatch
                      repair (MMR) gene. Recent studies show an increased
                      prevalence of LS among children with cancer, suggesting a
                      causal relationship. For LS-spectrum (LSS) cancers,
                      including high-grade gliomas and colorectal cancer,
                      causality has been supported by typical MMR-related tumor
                      characteristics, but for non-LSS cancers, causality is
                      unclear. We characterized 20 malignant tumors of 18 children
                      with LS, including 16 non-LSS tumors. We investigated second
                      hits, tumor mutational load, mutational signatures and MMR
                      protein expression. In all LSS tumors and three non-LSS
                      tumors, we detected MMR deficiency caused by second hit
                      somatic alterations. Furthermore, these MMR-deficient tumors
                      carried driver variants that likely originated as a
                      consequence of MMR deficiency. However, in 13 non-LSS tumors
                      $(81\%),$ a second hit and MMR deficiency were absent, thus
                      a causal link between LS and cancer development in these
                      children is lacking. These findings demonstrate that
                      causality of LS in children with cancer, which can be
                      determined by molecular tumor characterization, seems to be
                      restricted to specific tumor types. Large molecular and
                      epidemiological studies are needed to further refine the
                      tumor spectrum in children with LS.},
      keywords     = {Lynch syndrome (Other) / cancer predisposition (Other) /
                      mismatch repair (Other) / mutational signatures (Other) /
                      pediatric cancer (Other)},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38175816},
      doi          = {10.1002/ijc.34832},
      url          = {https://inrepo02.dkfz.de/record/286670},
}