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@ARTICLE{Rajtmajerova:304274,
      author       = {M. Rajtmajerova and F. Ambrozkiewicz and V. Hlavac and A.
                      Trailin and L. Cervenkova and J. Bruha and S. Susova and P.
                      Soucek and P. Vodicka and L. Vodickova and O. Kubecek and S.
                      Filip and V. R. Mallela and W. Ye and F. Zitricky and V.
                      Liska and K. Hemminki$^*$},
      title        = {{G}enetic differences between primary colorectal cancer and
                      its paired synchronous and metachronous metastases.},
      journal      = {International journal of cancer},
      volume       = {nn},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2025-01815},
      pages        = {nn},
      year         = {2025},
      note         = {#LA:Z999# / epub},
      abstract     = {As the second most deadly cancerous disease worldwide,
                      colorectal cancer (CRC) stands in the center of scientific
                      interest in hope to develop novel approaches for precise
                      diagnostics and prognosis determination. Metastatic disease
                      remains the main cause of CRC mortality. To investigate the
                      underlying genetic differences between CRC patients with
                      synchronous and metachronous liver metastases, we performed
                      whole-exome sequencing of 210 patient samples using
                      formalin-fixed paraffin-embedded samples from primary tumors
                      and the paired liver metastatic tissue. The analyses
                      included types and levels of mutations and copy number
                      variation. APC and TP53 were the most commonly mutated genes
                      in all samples with differing frequency between primary CRC
                      (both $50\%)$ and its metachronous metastasis (both $64\%).$
                      While MPDZ gene mutations were restricted to primary tumors
                      that developed metachronous metastases only, mutations in
                      VCAN, MTCL1, MDN1, SHROOM2, SPEG, and GLI2 were more
                      prevalent in primary tumors giving rise to synchronous
                      metastases. FBN1 mutations were unique to synchronous liver
                      metastatic tissue. Analysis of genetic interactions revealed
                      different associations between mutated genes in patients
                      with tumors of different chronicity, including driver genes
                      such as TP53, which was associated with APC in synchronous
                      patients, while in primary tumors with metachronous
                      metastases it co-occurs with mutations in NBPF11 and
                      PRAMEF15, respectively. The results suggest that distinct
                      tumor progression pathways account for different chronicity
                      outcomes further affecting patients' survival. However,
                      larger studies are needed incorporating transcriptomic and
                      epigenomic data to shed further light on the mechanistic
                      chain from mutations to downstream gene expression
                      regulation.},
      keywords     = {WES (Other) / colorectal cancer (Other) / metachronous
                      liver metastasis (Other) / synchronous liver metastasis
                      (Other) / whole‐exome sequencing (Other)},
      cin          = {Z999},
      ddc          = {610},
      cid          = {I:(DE-He78)Z999-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40884237},
      doi          = {10.1002/ijc.70116},
      url          = {https://inrepo02.dkfz.de/record/304274},
}