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@ARTICLE{Lefler:302807,
      author       = {D. S. Lefler and A. Elliott and W. Jiang and U.
                      Martinez-Outschoorn and J. Al-Sabah and D. M. Freed and C.
                      M. King and R. G. Maki and R. F. Riedel and J. F. Modiano
                      and D. Hübschmann$^*$ and H. Glimm$^*$ and S. Fröhling$^*$
                      and M. Oberley and S. A. Boikos and A. Basu Mallick},
      title        = {{P}ansarcoma {A}nalysis of {C}yclin-{D}ependent {K}inase
                      and {C}yclin {O}utlier {G}ene {E}xpression {H}ighlights
                      {CDK}7 as a {P}otential {T}herapeutic {T}arget in
                      {C}hordoma},
      journal      = {JCO precision oncology},
      volume       = {9},
      issn         = {2473-4284},
      address      = {Alexandria, VA},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2025-01347},
      pages        = {e2500149},
      year         = {2025},
      note         = {2025 Jul:9:e2500149},
      abstract     = {Purpose: Cyclin-dependent kinase (CDK)4/6 inhibitors are
                      approved for the treatment of breast cancer, and they have
                      more recently been used in patients with
                      well-differentiated/dedifferentiated liposarcomas
                      (WD-LPSs/DD-LPSs). However, targeting of these and other
                      CDKs, including transcriptional CDKs, remains a promising
                      avenue of investigation for various cancers. Therefore, we
                      sought to characterize outlier overexpression of CDK and
                      cyclin genes in sarcomas. On the basis of the initial
                      results, further studies were undertaken to investigate the
                      roles of CDK7 and CDK18 in chordomas.Materials and methods:
                      An initial analysis of CDK/cyclin gene expression involved
                      an American national biomarker database of deidentified
                      patients (Caris Life Sciences, Phoenix, AZ; n = 3,757) using
                      novel, strict definitions to identify outlier overexpressing
                      samples across subtypes. Results were validated with a
                      German national database (Molecularly Aided Stratification
                      for Tumor Eradication Research [MASTER]; n = 943). Outlier
                      overexpression for CDK7/18 in chordoma was compared with
                      immunohistochemical (IHC) expression using tissue
                      microarrays, and a selective investigational CDK7 inhibitor
                      was tested against four chordoma cell lines.Results: Initial
                      analysis identified expected findings (eg, outlier
                      overexpression of CDK4 in $39\%-66\%$ of WD-LPSs/DD-LPSs),
                      clinical correlates of fundamental scientific work (eg,
                      CCND1 in $29\%$ of Ewing sarcomas), and novel associations
                      (eg, CDK7/CDK18 in $42\%/37\%$ of chordomas). Outlier
                      overexpression for CDK7 and CDK18 in chordomas was
                      corroborated in the MASTER database $(40\%$ and $26\%$ of
                      patients, respectively). IHC analysis confirmed strong and
                      diffuse expression of both CDK7 and CDK18 in chordoma
                      samples. Furthermore, CDK7 inhibition was highly effective
                      in four chordoma cell lines.Conclusion: This study supports
                      further investigation into targeting of CDKs and cyclins in
                      select sarcoma subtypes, and it specifically suggests a
                      therapeutic approach inhibiting CDK7 in chordoma.},
      cin          = {W015 / HD01 / B340 / B280},
      ddc          = {610},
      cid          = {I:(DE-He78)W015-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B340-20160331 / I:(DE-He78)B280-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40601892},
      doi          = {10.1200/PO-25-00149},
      url          = {https://inrepo02.dkfz.de/record/302807},
}