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@ARTICLE{Wiestler:128541,
      author       = {B. P. O. Wiestler$^*$ and D. Capper$^*$ and M. Sill$^*$ and
                      D. Jones$^*$ and V. Hovestadt$^*$ and D. Sturm$^*$ and C.
                      Koelsche$^*$ and A. Bertoni$^*$ and L. Schweizer$^*$ and A.
                      Korshunov$^*$ and E. K. Weiß$^*$ and M. Schliesser$^*$ and
                      A. Radbruch$^*$ and C. Herold-Mende$^*$ and P. Roth and A.
                      Unterberg and C. Hartmann$^*$ and T. Pietsch and G.
                      Reifenberger$^*$ and P. Lichter$^*$ and B. Radlwimmer$^*$
                      and M. Platten$^*$ and S. Pfister$^*$ and A. von
                      Deimling$^*$ and M. Weller and W. Wick$^*$},
      title        = {{I}ntegrated {DNA} methylation and copy-number profiling
                      identify three clinically and biologically relevant groups
                      of anaplastic glioma.},
      journal      = {Acta neuropathologica},
      volume       = {128},
      number       = {4},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-04557},
      pages        = {561 - 571},
      year         = {2014},
      abstract     = {The outcome of patients with anaplastic gliomas varies
                      considerably. Whether a molecular classification of
                      anaplastic gliomas based on large-scale genomic or
                      epigenomic analyses is superior to histopathology for
                      reflecting distinct biological groups, predicting outcomes
                      and guiding therapy decisions has yet to be determined.
                      Epigenome-wide DNA methylation analysis, using a platform
                      which also allows the detection of copy-number aberrations,
                      was performed in a cohort of 228 patients with anaplastic
                      gliomas (astrocytomas, oligoastrocytomas, and
                      oligodendrogliomas), including 115 patients of the NOA-04
                      trial. We further compared these tumors with a group of 55
                      glioblastomas. Unsupervised clustering of DNA methylation
                      patterns revealed two main groups correlated with IDH
                      status: CpG island methylator phenotype (CIMP) positive
                      $(77.5 \%)$ or negative $(22.5 \%).$ CIMP(pos) (IDH
                      mutant) tumors showed a further separation based on
                      copy-number status of chromosome arms 1p and 19q. CIMP(neg)
                      (IDH wild type) tumors showed hallmark copy-number
                      alterations of glioblastomas, and clustered together with
                      CIMP(neg) glioblastomas without forming separate groups
                      based on WHO grade. Notably, there was no molecular evidence
                      for a distinct biological entity representing anaplastic
                      oligoastrocytoma. Tumor classification based on CIMP and
                      1p/19q status was significantly associated with survival,
                      allowing a better prediction of outcome than the current
                      histopathological classification: patients with CIMP(pos)
                      tumors with 1p/19q codeletion (CIMP-codel) had the best
                      prognosis, followed by patients with CIMP(pos) tumors but
                      intact 1p/19q status (CIMP-non-codel). Patients with
                      CIMP(neg) anaplastic gliomas (GBM-like) had the worst
                      prognosis. Collectively, our data suggest that anaplastic
                      gliomas can be grouped by IDH and 1p/19q status into three
                      molecular groups that show clear links to underlying biology
                      and a significant association with clinical outcome in a
                      prospective trial cohort.},
      keywords     = {Nuclear Proteins (NLM Chemicals) / Tumor Suppressor
                      Proteins (NLM Chemicals) / DNA Modification Methylases (NLM
                      Chemicals) / MGMT protein, human (NLM Chemicals) /
                      Telomerase (NLM Chemicals) / DNA Helicases (NLM Chemicals) /
                      ATRX protein, human (NLM Chemicals) / DNA Repair Enzymes
                      (NLM Chemicals)},
      cin          = {G370 / G380 / C060 / B062 / B060 / L101 / L401 / E012},
      ddc          = {610},
      cid          = {I:(DE-He78)G370-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)C060-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)B060-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L401-20160331 / I:(DE-He78)E012-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25008768},
      doi          = {10.1007/s00401-014-1315-x},
      url          = {https://inrepo02.dkfz.de/record/128541},
}