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@ARTICLE{Gojo:128032,
      author       = {J. Gojo and D. Lötsch and S. Spiegl-Kreinecker and K.
                      Pajtler$^*$ and K. Neumayer and P. Korbel and A. Araki and
                      A. Brandstetter and T. Mohr and V. Hovestadt$^*$ and L.
                      Chavez$^*$ and D. Kirchhofer and G. Ricken and H. Stefanits
                      and A. Korshunov$^*$ and S. Pfister$^*$ and K. Dieckmann and
                      A. A. Azizi and T. Czech and M. Filipits and M. Kool$^*$ and
                      A. Peyrl and I. Slavc and W. Berger and C. Haberler},
      title        = {{T}elomerase activation in posterior fossa group {A}
                      ependymomas is associated with dismal prognosis and
                      chromosome 1q gain.},
      journal      = {Neuro-Oncology},
      volume       = {19},
      number       = {9},
      issn         = {1523-5866},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2017-04054},
      pages        = {1183 - 1194},
      year         = {2017},
      abstract     = {Ependymomas account for up to $10\%$ of childhood CNS
                      tumors and have a high rate of tumor recurrence despite
                      gross total resection. Recently, classification into
                      molecular ependymoma subgroups has been established, but the
                      mechanisms underlying the aggressiveness of certain subtypes
                      remain widely enigmatic. The aim of this study was to
                      dissect the clinical and biological role of telomerase
                      reactivation, a frequent mechanism of cancer cells to evade
                      cellular senescence, in pediatric ependymoma.We determined
                      telomerase enzymatic activity, hTERT mRNA expression,
                      promoter methylation, and the rs2853669 single nucleotide
                      polymorphism located in the hTERT promoter in a
                      well-characterized cohort of pediatric intracranial
                      ependymomas.In posterior fossa ependymoma group A (PF-EPN-A)
                      tumors, telomerase activity varied and was significantly
                      associated with dismal overall survival, whereas telomerase
                      reactivation was present in all supratentorial RelA
                      fusion-positive (ST-EPN-RELA) ependymomas. In silico
                      analysis of methylation patterns showed that only these two
                      subgroups harbor hypermethylated hTERT promoters suggesting
                      telomerase reactivation via epigenetic mechanisms.
                      Furthermore, chromosome 1q gain, a well-known negative
                      prognostic factor, was strongly associated with telomerase
                      reactivation in PF-EPN-A. Additional in silico analyses of
                      gene expression data confirmed this finding and further
                      showed enrichment of the E-twenty-six factor, Myc, and E2F
                      target genes in 1q gained ependymomas. Additionally, 1q
                      gained tumors showed elevated expression of ETV3, an
                      E-twenty-six factor gene located on chromosome 1q.Taken
                      together we describe a subgroup-specific impact of
                      telomerase reactivation on disease progression in pediatric
                      ependymoma and provide preliminary evidence for the involved
                      molecular mechanisms.},
      cin          = {B062 / G380 / B060 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)B060-20160331 / I:(DE-He78)L101-20160331},
      pnm          = {319H - Addenda (POF3-319H)},
      pid          = {G:(DE-HGF)POF3-319H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28371821},
      pmc          = {pmc:PMC5570194},
      doi          = {10.1093/neuonc/nox027},
      url          = {https://inrepo02.dkfz.de/record/128032},
}