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@ARTICLE{Bayraktar:298981,
      author       = {R. Bayraktar and Y. Tang and M.-P. Dragomir$^*$ and C. Ivan
                      and X. Peng and L. Fabris and J. Zhang and A. Carugo and S.
                      Aneli and J. Liu and M. M. Chen and S. Srinivasan and I.
                      Sahnoune and E. Bayraktar and K. C. Akdemir and M. Chen and
                      P. Narayanan and W. Huang and L. F. Ott and A. K. Eterovic
                      and O. E. Villarreal and M. M. Mohammad and M. D. Peoples
                      and D. M. Walsh and J. A. Hernandez and M. B. Morgan and K.
                      R. Shaw and J. S. Davis and D. Menter and C. S. Tam and P.
                      Yeh and S.-J. Dawson and L. Z. Rassenti and T. J. Kipps and
                      T. Kunej and Z. Estrov and S. A. Joosse and L. Pagani and C.
                      Alix-Panabières and K. Pantel and A. Ferajoli and A.
                      Futreal and I. I. Wistuba and M. Radovich and S. Kopetz and
                      M. J. Keating and G. F. Draetta and J. S. Mattick and H.
                      Liang and G. A. Calin},
      title        = {{T}he mutational landscape and functional effects of
                      noncoding ultraconserved elements in human cancers.},
      journal      = {Science advances},
      volume       = {11},
      number       = {8},
      issn         = {2375-2548},
      address      = {Washington, DC [u.a.]},
      publisher    = {Assoc.},
      reportid     = {DKFZ-2025-00401},
      pages        = {eado2830},
      year         = {2025},
      abstract     = {The mutational landscape of phylogenetically ultraconserved
                      elements (UCEs), especially those in noncoding DNAs
                      (ncUCEs), and their functional relevance in cancers remain
                      poorly characterized. Here, we perform a systematic analysis
                      of whole-genome and in-house targeted UCE sequencing
                      datasets from more than 3000 patients with cancer of 13,736
                      UCEs and demonstrate that ncUCE somatic alterations are
                      common. Using a multiplexed CRISPR knockout screen in
                      colorectal cancer cells, we show that the loss of several
                      altered ncUCEs significantly affects cell proliferation.
                      In-depth functional studies in vitro and in vivo further
                      reveal that specific ncUCEs can be enhancers of tumor
                      suppressors (such as ARID1B) and silencers of oncogenic
                      proteins (such as RPS13). Moreover, several miRNAs located
                      in ncUCEs are recurrently mutated. Mutations in miR-142
                      locus can affect the Drosha-mediated processing of precursor
                      miRNAs, resulting in the down-regulation of the mature
                      transcript. These results provide systematic evidence that
                      specific ncUCEs play diverse regulatory roles in cancer.},
      keywords     = {Humans / Mutation / Neoplasms: genetics / Conserved
                      Sequence / MicroRNAs: genetics / Cell Line, Tumor / Gene
                      Expression Regulation, Neoplastic / RNA, Untranslated:
                      genetics / Cell Proliferation: genetics / Animals / Mice /
                      MicroRNAs (NLM Chemicals) / RNA, Untranslated (NLM
                      Chemicals)},
      cin          = {BE01},
      ddc          = {500},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39970212},
      doi          = {10.1126/sciadv.ado2830},
      url          = {https://inrepo02.dkfz.de/record/298981},
}