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@ARTICLE{Richter:306609,
      author       = {G. H. S. Richter$^*$ and A. Ranft$^*$ and M. Kerkhoff$^*$
                      and M. Jens$^*$ and I. E. Kirchberg$^*$ and U. Dirksen$^*$},
      title        = {{T}he {P}uzzle of {G}enetic {S}tability and {C}hromosomal
                      {C}opy {N}umber {A}lterations for the {T}herapy of {E}wing
                      {S}arcoma.},
      journal      = {Cancers},
      volume       = {17},
      number       = {22},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2025-02646},
      pages        = {3719},
      year         = {2025},
      abstract     = {Studies of the genomic stability of Ewing sarcoma (EwS)
                      have produced contradictory findings. While they are
                      generally characterized by low mutation rates of individual
                      genes, several cases exhibit genomic alterations that
                      manifest as chromosomal gains and losses. Taken together,
                      these alterations represent independent biomarkers for EwS,
                      such as loss of heterozygosity (LOH) or an altered genome.
                      Patients with primary EwS tumors with fewer than three copy
                      number alterations (CNAs) have a better prognosis than those
                      with more CNAs. The functional mechanisms underlying this
                      chromosomal instability are not yet clear. However, there
                      are indications that this may be directly caused by the
                      EWSR1::ETS translocations that are characteristic of EwS.
                      The transcriptional behavior of the chimeric transcription
                      factor EWSR1-FLI1 leads to the formation of R-loop DNA-RNA
                      hybrids that form when RNA binds back to DNA during
                      transcription and increased replication stress, which may
                      result in structural chromosomal changes. Additionally, the
                      formation of EWSR1 fusion genes in EwS results in the loss
                      of one or both wild-type EWSR1 alleles in sarcoma cells. As
                      chromosome segregation has been observed under loss of
                      wild-type EWSR1, EWSR1 loss has been proposed as a potential
                      source of LOH. So, it is highly probable that a chromosomal
                      translocation and the subsequent formation of the EWSR1-ETS
                      fusion protein cause the genomic alterations in EwS. This
                      indicates that targeted therapy should be directed against
                      the CNA and LOH biology caused by the fusion protein.},
      subtyp        = {Review Article},
      keywords     = {EWSR1 haploinsufficiency (Other) / Ewing sarcoma (Other) /
                      biomarker (Other) / loss of heterozygosity (Other) /
                      replication stress (Other) / replication stress directed
                      therapy (Other)},
      cin          = {BE01 / ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331 / I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41301081},
      doi          = {10.3390/cancers17223719},
      url          = {https://inrepo02.dkfz.de/record/306609},
}