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@ARTICLE{Goeppert:305552,
      author       = {B. Goeppert and A. Charbel and R. Toth and Y. Zhang and D.
                      Tabbakh and T. Albrecht and D. Schrimpf$^*$ and L. de
                      Mestier and J. Cros and M. N. Vogel and D.-H. Chang and
                      E.-M. Bohn and A. Brobeil and J. Ji and S. Singer and P. V.
                      Nazarov and A. Perren and L. Apostolidis and A. von
                      Deimling$^*$ and S. Roessler},
      title        = {{DNA} methylation patterns facilitate tracing the origin of
                      neuroendocrine neoplasms.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-02222},
      pages        = {9477},
      year         = {2025},
      abstract     = {Neuroendocrine neoplasms (NEN) are thought to originate
                      from diffuse neuroendocrine networks and therefore most
                      frequently arise in the gastrointestinal tract and lungs.
                      The liver is a frequent site of metastasis of NEN but also
                      the existence of primary hepatic NEN has been proposed. Due
                      to the impact on disease management, it is urgently required
                      to discriminate the origin of hepatic NEN metastases and to
                      identify clinically relevant subgroups. Using a
                      comprehensive set of NEN (N = 212) from two independent
                      cohorts, we show that the DNA methylation profiles of NEN of
                      distinct anatomical localizations differ significantly and
                      primary tumor-metastasis pairs cluster together, enabling
                      the identification of the tumor origin. Furthermore, the
                      subgroup of hepatic NEN without clinically detectable
                      primary tumor, thus classified as primary hepatic NEN, does
                      not form a distinct cluster by DNA methylation analysis but
                      colocalizes with various subgroups of extrahepatic NEN.
                      Organ-specific subtyping of NEN delineates a foregut-like
                      epigenetic profile for hepatic NEN with unknown primary. We
                      propose a classifier with high prediction accuracy for each
                      of the different organ sites. In conclusion, our results
                      demonstrate that DNA methylation profiling enables precise
                      prediction of NEN origin and suggests that a substantial
                      proportion of presumed primary hepatic NEN may in fact
                      represent misclassified secondary hepatic NEN of unknown
                      primary.},
      keywords     = {Humans / DNA Methylation / Neuroendocrine Tumors: genetics
                      / Neuroendocrine Tumors: pathology / Liver Neoplasms:
                      genetics / Liver Neoplasms: secondary / Female / Male /
                      Middle Aged / Aged / Epigenesis, Genetic / Adult /
                      Neoplasms, Unknown Primary: genetics / Neoplasms, Unknown
                      Primary: pathology},
      cin          = {B300 / HD01},
      ddc          = {500},
      cid          = {I:(DE-He78)B300-20160331 / 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:41145514},
      doi          = {10.1038/s41467-025-65227-8},
      url          = {https://inrepo02.dkfz.de/record/305552},
}