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@ARTICLE{Reinhardt:136789,
      author       = {A. Reinhardt$^*$ and D. Stichel$^*$ and D. Schrimpf$^*$ and
                      F. Sahm$^*$ and A. Korshunov$^*$ and D. E. Reuss$^*$ and C.
                      Koelsche$^*$ and K. Huang$^*$ and A. K. Wefers$^*$ and V.
                      Hovestadt$^*$ and M. Sill$^*$ and D. Gramatzki and J.
                      Felsberg and G. Reifenberger and A. Koch and U.-W. Thomale
                      and A. Becker and V. H. Hans and M. Prinz and O. Staszewski
                      and T. Acker and H. Dohmen and C. Hartmann and W. Mueller
                      and M. S. A. Tuffaha and W. Paulus and K. Heß and B.
                      Brokinkel and J. Schittenhelm and C.-M. Monoranu and A. F.
                      Kessler and M. Loehr and R. Buslei and M. Deckert and C.
                      Mawrin and P. Kohlhof and E. Hewer and A. Olar and F. J.
                      Rodriguez and C. Giannini and A. A. NageswaraRao and U.
                      Tabori and N. M. Nunes and M. Weller and U. Pohl and Z.
                      Jaunmuktane and S. Brandner and A. Unterberg and D. Hänggi
                      and M. Platten$^*$ and S. Pfister$^*$ and W. Wick$^*$ and C.
                      Herold-Mende and D. Jones$^*$ and A. von Deimling$^*$ and D.
                      Capper$^*$},
      title        = {{A}naplastic astrocytoma with piloid features, a novel
                      molecular class of {IDH} wildtype glioma with recurrent
                      {MAPK} pathway, {CDKN}2{A}/{B} and {ATRX} alterations.},
      journal      = {Acta neuropathologica},
      volume       = {136},
      number       = {2},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2018-01227},
      pages        = {273 - 291},
      year         = {2018},
      abstract     = {Tumors with histological features of pilocytic astrocytoma
                      (PA), but with increased mitotic activity and additional
                      high-grade features (particularly microvascular
                      proliferation and palisading necrosis) have often been
                      designated anaplastic pilocytic astrocytomas. The status of
                      these tumors as a separate entity has not yet been
                      conclusively demonstrated and molecular features have only
                      been partially characterized. We performed DNA methylation
                      profiling of 102 histologically defined anaplastic pilocytic
                      astrocytomas. T-distributed stochastic
                      neighbor-embedding (t-SNE) and hierarchical clustering
                      analysis of these 102 cases against 158 reference cases from
                      12 glioma reference classes revealed that a subset of 83 of
                      these tumors share a common DNA methylation profile that is
                      distinct from the reference classes. These 83 tumors were
                      thus denominated DNA methylation class anaplastic
                      astrocytoma with piloid features (MC AAP). The 19 remaining
                      tumors were distributed amongst the reference classes, with
                      additional testing confirming the molecular diagnosis in
                      most cases. Median age of patients with MC AAP was
                      41.5 years. The most frequent localization was the
                      posterior fossa $(74\%).$ Deletions of CDKN2A/B (66/83,
                      $80\%),$ MAPK pathway gene alterations (49/65, $75\%,$ most
                      frequently affecting NF1, followed by BRAF and FGFR1) and
                      mutations of ATRX or loss of ATRX expression (33/74, $45\%)$
                      were the most common molecular alterations. All tumors were
                      IDH1/2 wildtype. The MGMT promoter was methylated in 38/83
                      tumors $(45\%).$ Outcome analysis confirmed an unfavorable
                      clinical course in comparison to PA, but better than IDH
                      wildtype glioblastoma. In conclusion, we show that a subset
                      of histologically defined anaplastic pilocytic astrocytomas
                      forms a separate DNA methylation cluster, harbors recurrent
                      alterations in MAPK pathway genes in combination with
                      alterations of CDKN2A/B and ATRX, affects patients who are
                      on average older than those diagnosed with PA and has an
                      intermediate clinical outcome.},
      cin          = {G380 / B060 / L101 / L401 / G160 / B062 / G702 / L201},
      ddc          = {610},
      cid          = {I:(DE-He78)G380-20160331 / I:(DE-He78)B060-20160331 /
                      I:(DE-He78)L101-20160331 / I:(DE-He78)L401-20160331 /
                      I:(DE-He78)G160-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)G702-20160331 / I:(DE-He78)L201-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29564591},
      doi          = {10.1007/s00401-018-1837-8},
      url          = {https://inrepo02.dkfz.de/record/136789},
}