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@ARTICLE{Mhrmann:299861,
      author       = {L. Möhrmann$^*$ and L. Rostock and M. Werner$^*$ and M.
                      Oleś$^*$ and J. Arnold$^*$ and N. Paramasivam$^*$ and K.
                      Jöhrens and L. Rupp and M. Schmitz and D. Richter and S.
                      Uhrig$^*$ and M. A. Fröhlich$^*$ and B. Hutter$^*$ and J.
                      Hüllein$^*$ and A. Jahn$^*$ and M. Arlt$^*$ and E. E.
                      Möhrmann$^*$ and D. Hanf$^*$ and L. Gieldon and S.
                      Kreutzfeldt$^*$ and C. E. Heilig$^*$ and M.-V. Teleanu$^*$
                      and D. B. Lipka and K. Beck and A. Baude-Müller$^*$ and A.
                      Mock and I. Jelas and D. T. Rieke and M. Wiesweg and C.
                      Brandts$^*$ and M. Boerries and A. L. Illert and A.
                      Desuki$^*$ and T. Kindler$^*$ and A. M. Krackhardt and C. B.
                      Westphalen and P. Christopoulos and L. Apostolidis and A.
                      Stenzinger and M. Allgäuer and O. Neumann and I. Kerle$^*$
                      and P. Horak$^*$ and C. Heining$^*$ and H. Grosch and E.
                      Schröck$^*$ and D. Hübschmann$^*$ and S. Fröhling$^*$ and
                      H. Glimm},
      title        = {{G}enomic landscape and molecularly informed therapy in
                      thymic carcinoma and other advanced thymic epithelial
                      tumors.},
      journal      = {Med},
      volume       = {6},
      number       = {6},
      issn         = {2666-6340},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-00591},
      pages        = {100612},
      year         = {2025},
      note         = {#LA:B340#LA:B280#LA:W015 / 2025 Jun 13;6(6):100612/
                      Computational Oncology Group (CO), Molecular Precision
                      Oncology Program (MPOP), German Cancer Research Center
                      (DKFZ), translational Functional Cancer Genomics, DKFZ
                      Heidelberg, Heidelberg, Germany, Innovation and Service
                      Unit, German Cancer Research Center (DKFZ), Heidelberg,
                      Germany},
      abstract     = {Thymic epithelial tumors (TETs) are rare malignancies with
                      limited treatment options and underexplored molecular
                      features.We examined the genomic landscape and therapeutic
                      outcomes in 81 patients with advanced TETs, including thymic
                      carcinomas (TCs), thymomas, and thymic neuroendocrine
                      neoplasms (TNENs), who were enrolled in the MASTER trial, a
                      prospective observational precision oncology trial.Using
                      whole-genome-sequencing and whole-exome-sequencing analysis,
                      transcriptome analysis, and methylome analysis, we
                      identified distinct molecular features across TET subtypes,
                      including a higher tumor mutational burden in TC and
                      pathogenic germline variants in $18\%$ of cases. We
                      performed transcriptome- and methylome-based unsupervised
                      clustering and were able to divide TCs into immunologically
                      hot and cold subsets, with hot TCs exhibiting higher T cell
                      infiltration and significantly longer overall survival. In
                      65 out of 76 $(86\%)$ patients, we recommended molecularly
                      informed therapies, which were applied in 29 out of 65
                      $(45\%)$ cases, leading to a disease control rate of $62\%$
                      and an objective response rate of $23\%$ (both n = 26). The
                      progression-free survival ratio (PFSr) was > 1.3 in 8 out of
                      24 $(33\%)$ patients, 7 of them having TC. Among TCs,
                      patients achieved a mean PFSr of 1.4, indicating potential
                      therapeutic advantages in this subgroup. The PFSr between
                      the PFS of immune checkpoint inhibition and preceding
                      therapies was significantly higher in the hot cluster
                      compared to the cold cluster (median 1.7 vs. 0.3; p =
                      0.01945).Our findings expand the understanding of TET
                      biology and emphasize the role of precision oncology in
                      informing treatment decisions and improving outcomes for
                      patients with advanced TETs, particularly in TCs.},
      keywords     = {Translation to patients (Other) / molecular profiling
                      (Other) / multiomics (Other) / precision oncology (Other) /
                      prospective observational study (Other) / targeted therapy
                      (Other) / thymic carcinoma (Other) / thymic epithelial tumor
                      (Other) / thymic neuroendocrine neoplasm (Other) / thymoma
                      (Other) / whole-genome sequencing (Other)},
      cin          = {DD01 / B340 / FM01 / HD01 / B280 / W015},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331 / I:(DE-He78)B340-20160331 /
                      I:(DE-He78)FM01-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B280-20160331 / I:(DE-He78)W015-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40107270},
      doi          = {10.1016/j.medj.2025.100612},
      url          = {https://inrepo02.dkfz.de/record/299861},
}