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@ARTICLE{Mack:131790,
      author       = {S. C. Mack and K. Pajtler$^*$ and L. Chavez$^*$ and K.
                      Okonechnikov$^*$ and K. C. Bertrand and X. Wang and S.
                      Erkek$^*$ and A. Federation and A. Song and C. Lee and X.
                      Wang and L. McDonald and J. J. Morrow and A. Saiakhova and
                      P. Sin-Chan and Q. Wu and K. A. Michaelraj and T. E. Miller
                      and C. G. Hubert and M. Ryzhova and L. Garzia and L. Donovan
                      and S. Dombrowski and D. C. Factor and B. Luu and C. L. L.
                      Valentim and R. C. Gimple and A. Morton and L. Kim and B. C.
                      Prager and J. J. Y. Lee and X. Wu and J. Zuccaro and Y.
                      Thompson and B. L. Holgado and J. Reimand and S. Q. Ke and
                      A. Tropper and S. Lai and S. Vijayarajah and S. Doan and V.
                      Mahadev and A. F. Miñan and S. Gröbner$^*$ and M. Lienhard
                      and M. Zapatka$^*$ and Z. Huang$^*$ and K. D. Aldape and A.
                      M. Carcaboso and P. J. Houghton and S. T. Keir and T.
                      Milde$^*$ and H. Witt$^*$ and Y. Li and C.-J. Li and X.-W.
                      Bian and D. Jones$^*$ and I. Scott and S. K. Singh and A.
                      Huang and P. B. Dirks and E. Bouffet and J. E. Bradner and
                      V. Ramaswamy and N. Jabado and J. T. Rutka and P. A.
                      Northcott and M. Lupien and P. Lichter$^*$ and A.
                      Korshunov$^*$ and P. C. Scacheri and S. Pfister$^*$ and M.
                      Kool$^*$ and M. D. Taylor and J. N. Rich},
      title        = {{T}herapeutic targeting of ependymoma as informed by
                      oncogenic enhancer profiling.},
      journal      = {Nature},
      volume       = {553},
      number       = {7686},
      issn         = {1476-4687},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2018-00087},
      pages        = {101 - 105},
      year         = {2018},
      abstract     = {Genomic sequencing has driven precision-based oncology
                      therapy; however, the genetic drivers of many malignancies
                      remain unknown or non-targetable, so alternative approaches
                      to the identification of therapeutic leads are necessary.
                      Ependymomas are chemotherapy-resistant brain tumours, which,
                      despite genomic sequencing, lack effective molecular
                      targets. Intracranial ependymomas are segregated on the
                      basis of anatomical location (supratentorial region or
                      posterior fossa) and further divided into distinct molecular
                      subgroups that reflect differences in the age of onset,
                      gender predominance and response to therapy. The most common
                      and aggressive subgroup, posterior fossa ependymoma group A
                      (PF-EPN-A), occurs in young children and appears to lack
                      recurrent somatic mutations. Conversely, posterior fossa
                      ependymoma group B (PF-EPN-B) tumours display frequent
                      large-scale copy number gains and losses but have favourable
                      clinical outcomes. More than $70\%$ of supratentorial
                      ependymomas are defined by highly recurrent gene fusions in
                      the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller
                      number involve fusion of the gene encoding the
                      transcriptional activator YAP1 (ST-EPN-YAP1).
                      Subependymomas, a distinct histologic variant, can also be
                      found within the supratetorial and posterior fossa
                      compartments, and account for the majority of tumours in the
                      molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we
                      describe mapping of active chromatin landscapes in 42
                      primary ependymomas in two non-overlapping primary
                      ependymoma cohorts, with the goal of identifying essential
                      super-enhancer-associated genes on which tumour cells
                      depend. Enhancer regions revealed putative oncogenes,
                      molecular targets and pathways; inhibition of these targets
                      with small molecule inhibitors or short hairpin RNA
                      diminished the proliferation of patient-derived neurospheres
                      and increased survival in mouse models of ependymomas.
                      Through profiling of transcriptional enhancers, our study
                      provides a framework for target and drug discovery in other
                      cancers that lack known genetic drivers and are therefore
                      difficult to treat.},
      subtyp        = {Letter},
      cin          = {B062 / L101 / B060 / G340 / G380},
      ddc          = {070},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)B060-20160331 / I:(DE-He78)G340-20160331 /
                      I:(DE-He78)G380-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29258295},
      doi          = {10.1038/nature25169},
      url          = {https://inrepo02.dkfz.de/record/131790},
}