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@ARTICLE{Bolduan:301583,
      author       = {F. Bolduan and N. Müller-Bötticher and O. Debnath and I.
                      Eichhorn and Y. Giesecke and A. Wetzel and S. Sahay and T.
                      Zemojtel and M. Jaeger and U. Ungethuem and C. Roderburg and
                      C. A. Kunze and A. Lehmann and D. Horst$^*$ and F. Tacke and
                      R. Eils and B. Wiedenmann and M. Sigal and N. Ishaque},
      title        = {{S}mall intestinal neuroendocrine tumors lack early genomic
                      drivers, acquire {DNA} repair defects and harbor hallmarks
                      of low {REST} expression.},
      journal      = {Scientific reports},
      volume       = {15},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-01091},
      pages        = {17969},
      year         = {2025},
      abstract     = {The tumorigenesis of small intestinal neuroendocrine tumors
                      (siNETs) is not understood and comprehensive genomic and
                      transcriptomic data sets are limited. Therefore, we
                      performed whole genome and transcriptome analysis of 39 well
                      differentiated siNET samples. Our genomic data revealed a
                      lack of recurrent driver mutations and demonstrated that
                      multifocal siNETs from individual patients can arise
                      genetically independently. We detected germline mutations in
                      Fanconi anemia DNA repair pathway (FANC) genes, involved in
                      homologous recombination (HR) DNA repair, in $9\%$ of
                      patients and found mutational signatures of defective HR DNA
                      repair in late-stage tumor evolution. Furthermore,
                      transcriptomic analysis revealed low expression of the
                      transcriptional repressor REST. Summarizing, we identify a
                      novel common transcriptomic signature of siNETs and
                      demonstrate that genomic alterations alone do not explain
                      initial tumor formation, while impaired DNA repair likely
                      contributes to tumor evolution and represents a potential
                      pharmaceutical target in a subset of patients.},
      keywords     = {Humans / Neuroendocrine Tumors: genetics / Neuroendocrine
                      Tumors: pathology / Neuroendocrine Tumors: metabolism /
                      Intestinal Neoplasms: genetics / Intestinal Neoplasms:
                      pathology / DNA Repair: genetics / Gene Expression
                      Regulation, Neoplastic / Female / Male / Repressor Proteins:
                      genetics / Repressor Proteins: metabolism / Intestine,
                      Small: pathology / Intestine, Small: metabolism / Gene
                      Expression Profiling / Middle Aged / Transcriptome /
                      Germ-Line Mutation / Genomics / Adult / Repressor Proteins
                      (NLM Chemicals)},
      cin          = {BE01},
      ddc          = {600},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40410286},
      pmc          = {pmc:PMC12102166},
      doi          = {10.1038/s41598-025-01912-4},
      url          = {https://inrepo02.dkfz.de/record/301583},
}