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@ARTICLE{Korshunov:128946,
      author       = {A. Korshunov$^*$ and D. Capper$^*$ and D. Reuss$^*$ and D.
                      Schrimpf and M. Ryzhova and V. Hovestadt$^*$ and D.
                      Sturm$^*$ and J. Meyer and C. Jones and O. Zheludkova and E.
                      Kumirova and A. Golanov and M. Kool$^*$ and U. Schüller$^*$
                      and M. Mittelbronn$^*$ and M. Hasselblatt and J.
                      Schittenhelm and G. Reifenberger$^*$ and C. Herold-Mende$^*$
                      and P. Lichter$^*$ and A. von Deimling$^*$ and S.
                      Pfister$^*$ and D. Jones$^*$},
      title        = {{H}istologically distinct neuroepithelial tumors with
                      histone 3 {G}34 mutation are molecularly similar and
                      comprise a single nosologic entity.},
      journal      = {Acta neuropathologica},
      volume       = {131},
      number       = {1},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-04958},
      pages        = {137 - 146},
      year         = {2016},
      abstract     = {In contrast to the relative morphological uniformity of
                      histone H3 K27-mutant high-grade gliomas, H3 G34-mutant
                      tumors present as a histopathologically heterogeneous group
                      of neoplasms, with microscopic characteristics typical of
                      either glioblastoma (GBM) or central nervous system
                      primitive neuroectodermal tumors (CNS-PNET). In the current
                      study, we performed an integrative clinical,
                      histopathological and molecular analysis of 81 G34-mutant
                      CNS tumors. Routinely prepared tumor tissues were
                      investigated for genomic and epigenomic alterations. Despite
                      their divergent histopathological appearance, CNS tumors
                      with H3.3 G34 mutations displayed uniform epigenetic
                      signatures, suggesting a single biological origin.
                      Comparative cytogenetic analysis with other GBM subtypes
                      disclosed a high frequency and high specificity of 3q and 4q
                      loss across G34-mutant tumors. PDGFRA amplification was more
                      common in cases with GBM than with PNET morphology (36 vs. 5
                      $\%,$ respectively), while CCND2 amplifications showed the
                      opposite trend (5 vs. 27 $\%).$ Survival analysis revealed
                      the presence of amplified oncogene(s) and MGMT methylation
                      as independent prognostic markers for poor and favorable
                      outcomes, respectively. No difference in outcome was found
                      between morphological variants (GBM vs. PNET). Thus,
                      different histological variants of G34-mutant CNS tumors
                      likely comprise a single biological entity (high-grade
                      glioma with H3 G34 mutation, $HGG_G34),$ which should be
                      outlined in future diagnostic and therapeutic
                      classifications. Screening for H3.3 G34 mutation should
                      therefore be recommended as a routine diagnostic marker for
                      supratentorial CNS tumors across a broad histological
                      spectrum.},
      keywords     = {Histones (NLM Chemicals)},
      cin          = {B062 / B060 / G380 / L101 / L401 / L501},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)B060-20160331 /
                      I:(DE-He78)G380-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L401-20160331 / I:(DE-He78)L501-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26482474},
      doi          = {10.1007/s00401-015-1493-1},
      url          = {https://inrepo02.dkfz.de/record/128946},
}