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@ARTICLE{Reuss:127373,
      author       = {D. E. Reuss$^*$ and F. Sahm$^*$ and D. Schrimpf$^*$ and B.
                      P. O. Wiestler$^*$ and D. Capper$^*$ and C. Koelsche$^*$ and
                      L. Schweizer$^*$ and A. Korshunov$^*$ and D. Jones$^*$ and
                      V. Hovestadt and M. Mittelbronn$^*$ and J. Schittenhelm and
                      C. Herold-Mende$^*$ and A. Unterberg$^*$ and M. Platten$^*$
                      and M. Weller and W. Wick$^*$ and S. Pfister$^*$ and A. von
                      Deimling$^*$},
      title        = {{ATRX} and {IDH}1-{R}132{H} immunohistochemistry with
                      subsequent copy number analysis and {IDH} sequencing as a
                      basis for an 'integrated' diagnostic approach for adult
                      astrocytoma, oligodendroglioma and glioblastoma.},
      journal      = {Acta neuropathologica},
      volume       = {129},
      number       = {1},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-03398},
      pages        = {133 - 146},
      year         = {2015},
      abstract     = {Diffuse gliomas are represented in the 2007 WHO
                      classification as astrocytomas, oligoastrocytomas and
                      oligodendrogliomas of grades II and III and glioblastomas
                      WHO grade IV. Molecular data on these tumors have a major
                      impact on prognosis and therapy of the patients.
                      Consequently, the inclusion of molecular parameters in the
                      WHO definition of brain tumors is being planned and has been
                      forwarded as the 'ISN-Haarlem' consensus. We, here, analyze
                      markers of special interest including ATRX, IDH and 1p/19q
                      codeletion in a series of 405 adult patients. Among the WHO
                      2007 classified tumors were 152 astrocytomas, 61
                      oligodendrogliomas, 63 oligoastrocytomas and 129
                      glioblastomas. Following the concepts of the 'ISN-Haarlem',
                      we rediagnosed the series to obtain 'integrated' diagnoses
                      with 155 tumors being astrocytomas, 100 oligodendrogliomas
                      and 150 glioblastomas. In a subset of 100 diffuse gliomas
                      from the NOA-04 trial with long-term follow-up data
                      available, the 'integrated' diagnosis had a significantly
                      greater prognostic power for overall and progression-free
                      survival compared to WHO 2007. Based on the 'integrated'
                      diagnoses, loss of ATRX expression was close to being
                      mutually exclusive to 1p/19q codeletion, with only 2 of 167
                      ATRX-negative tumors exhibiting 1p/19q codeletion. All but 4
                      of 141 patients with loss of ATRX expression and diffuse
                      glioma carried either IDH1 or IDH2 mutations. Interestingly,
                      the majority of glioblastoma patients with loss of ATRX
                      expression but no IDH mutations exhibited an H3F3A mutation.
                      Further, all patients with 1p/19 codeletion carried a
                      mutation in IDH1 or IDH2. We present an algorithm based on
                      stepwise analysis with initial immunohistochemistry for ATRX
                      and IDH1-R132H followed by 1p/19q analysis followed by IDH
                      sequencing which reduces the number of molecular analyses
                      and which has a far better association with patient outcome
                      than WHO 2007.},
      keywords     = {Nuclear Proteins (NLM Chemicals) / Isocitrate Dehydrogenase
                      (NLM Chemicals) / IDH1 protein, human (NLM Chemicals) / DNA
                      Helicases (NLM Chemicals) / ATRX protein, human (NLM
                      Chemicals)},
      cin          = {G380 / G370 / B062 / B060 / G160 / L101 / L501 / L801},
      ddc          = {610},
      cid          = {I:(DE-He78)G380-20160331 / I:(DE-He78)G370-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)B060-20160331 /
                      I:(DE-He78)G160-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L501-20160331 / I:(DE-He78)L801-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25427834},
      doi          = {10.1007/s00401-014-1370-3},
      url          = {https://inrepo02.dkfz.de/record/127373},
}