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@ARTICLE{Korshunov:128073,
      author       = {A. Korshunov$^*$ and D. Schrimpf$^*$ and M. Ryzhova and D.
                      Sturm$^*$ and L. Chavez$^*$ and V. Hovestadt$^*$ and T.
                      Sharma$^*$ and A. Habel$^*$ and A. Burford and C. Jones and
                      O. Zheludkova and E. Kumirova and C. M. Kramm and A. Golanov
                      and D. Capper$^*$ and A. von Deimling$^*$ and S. Pfister$^*$
                      and D. Jones$^*$},
      title        = {{H}3-/{IDH}-wild type pediatric glioblastoma is comprised
                      of molecularly and prognostically distinct subtypes with
                      associated oncogenic drivers.},
      journal      = {Acta neuropathologica},
      volume       = {134},
      number       = {3},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-04095},
      pages        = {507 - 516},
      year         = {2017},
      abstract     = {Pediatric glioblastoma (pedGBM) is an extremely aggressive
                      pediatric brain tumor, accounting $for ~6\%$ of all central
                      nervous system neoplasms in children. Approximately half of
                      pedGBM harbor recurrent somatic mutations in histone 3
                      variants or, infrequently, IDH1/2. The remaining subset of
                      pedGBM is highly heterogeneous, and displays a variety of
                      genomic and epigenetic features. In the current study, we
                      aimed to further stratify an H3-/IDH-wild type (wt) pedGBM
                      cohort assessed through genome-wide molecular profiling. As
                      a result, we identified three molecular subtypes of these
                      tumors, differing in their genomic and epigenetic signatures
                      as well as in their clinical behavior. We designated these
                      subtypes $pedGBM_MYCN$ (enriched for MYCN amplification),
                      $pedGBM_RTK1$ (enriched for PDGFRA amplification) and
                      $pedGBM_RTK2$ (enriched for EGFR amplification). These
                      molecular subtypes were associated with significantly
                      different outcomes, i.e. $pedGBM_RTK2$ tumors show a
                      significantly longer survival time (median OS 44 months),
                      $pedGBM_MYCN$ display extremely poor outcomes (median OS
                      14 months), and $pedGBM_RTK1$ tumors harbor an intermediate
                      prognosis. In addition, the various molecular subtypes of
                      H3-/IDH-wt pedGBM were clearly distinguishable from their
                      adult counterparts, underlining their biological
                      distinctiveness. In conclusion, our study demonstrates
                      significant molecular heterogeneity of H3-/IDH-wt pedGBM in
                      terms of DNA methylation and cytogenetic alterations. The
                      recognition of three molecular subtypes of H3-/IDH-wt pedGBM
                      further revealed close correlations with biological
                      parameters and clinical outcomes and may therefore, be
                      predictive of response to standard treatment protocols, but
                      could also be useful for stratification for novel,
                      molecularly based therapies.},
      cin          = {G380 / L101 / B062 / B060},
      ddc          = {610},
      cid          = {I:(DE-He78)G380-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)B060-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28401334},
      doi          = {10.1007/s00401-017-1710-1},
      url          = {https://inrepo02.dkfz.de/record/128073},
}