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@ARTICLE{Cosenza:305589,
      author       = {M. R. Cosenza and A. Gaiatto and B. Erarslan Uysal$^*$ and
                      Á. Andrades and N. L. Sautter and M. Simunovic and M. A.
                      Jendrusch and S. Zumalave and T. Rausch and A. Halavatyi and
                      E.-M. Geissen and J. L. Eigenmann and T. Weber and P.
                      Hasenfeld and E. Benito and C. Stober and I. Cortes-Ciriano
                      and A. Kulozik$^*$ and R. Pepperkok and J. Korbel$^*$},
      title        = {{O}rigins of chromosome instability unveiled by coupled
                      imaging and genomics.},
      journal      = {Nature},
      volume       = {nn},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2025-02248},
      pages        = {nn},
      year         = {2025},
      note         = {#LA:B480# / epub},
      abstract     = {Somatic chromosome instability results in widespread
                      structural and numerical chromosomal abnormalities (CAs)
                      during cancer evolution1-3. Although CAs have been linked to
                      mitotic errors resulting in the emergence of nuclear
                      atypia4-7, the underlying processes and rates of spontaneous
                      CA formation in human cells are underexplored. Here we
                      introduce machine-learning-assisted genomics and imaging
                      convergence (MAGIC)-an autonomously operated platform that
                      integrates live-cell imaging of micronucleated cells,
                      machine learning on-the-fly and single-cell genomics to
                      systematically investigate CA formation. Applying MAGIC to
                      near-diploid, non-transformed cell lines, we track de novo
                      CAs over successive cell cycles, highlighting the common
                      role of dicentric chromosomes as initiating events. We
                      determine the baseline CA mutation rate, which approximately
                      doubles in TP53-deficient cells, and observe that chromosome
                      losses arise more frequently than gains. The targeted
                      induction of DNA double-strand breaks along chromosome arms
                      triggers distinct CA processes, revealing stable
                      isochromosomes, coordinated segregation and amplification of
                      isoacentric segments in multiples of two, as well as complex
                      CA outcomes, influenced by the chromosomal break location.
                      Our data contrast de novo CA spectra from somatic mutational
                      landscapes after selection occurred. The experimentation
                      enabled by MAGIC advances the dissection of DNA
                      rearrangement processes, shedding light on fundamental
                      determinants of chromosomal instability.},
      cin          = {A400 / B480},
      ddc          = {500},
      cid          = {I:(DE-He78)A400-20160331 / I:(DE-He78)B480-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41162705},
      doi          = {10.1038/s41586-025-09632-5},
      url          = {https://inrepo02.dkfz.de/record/305589},
}