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@ARTICLE{Koelsche:131057,
      author       = {C. Koelsche$^*$ and D. Schrimpf$^*$ and L. Tharun and E.
                      Roth and D. Sturm$^*$ and D. Jones$^*$ and E.-K. Renker and
                      M. Sill$^*$ and A. Baude$^*$ and F. Sahm$^*$ and D.
                      Capper$^*$ and M. Bewerunge-Hudler$^*$ and W. Hartmann and
                      A. E. Kulozik and I. Petersen and U. Flucke and H. W. B.
                      Schreuder and R. Büttner and M.-A. Weber and P. Schirmacher
                      and C. Plass$^*$ and S. Pfister$^*$ and A. von Deimling$^*$
                      and G. Mechtersheimer},
      title        = {{H}istone 3.3 hotspot mutations in conventional
                      osteosarcomas: a comprehensive clinical and molecular
                      characterization of six {H}3{F}3{A} mutated cases.},
      journal      = {Clinical Sarcoma Research},
      volume       = {7},
      number       = {1},
      issn         = {2045-3329},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2017-06124},
      pages        = {9},
      year         = {2017},
      abstract     = {Histone 3.3 (H3.3) hotspot mutations in bone tumors occur
                      in the vast majority of giant cell tumors of bone (GCTBs;
                      $96\%),$ chondroblastomas $(95\%)$ and in a few cases of
                      osteosarcomas. However, clinical presentation,
                      histopathological features, and additional molecular
                      characteristics of H3.3 mutant osteosarcomas are largely
                      unknown.In this multicentre, retrospective study, a total of
                      106 conventional high-grade osteosarcomas, across all age
                      groups were re-examined for hotspot mutations in the H3.3
                      coding genes H3F3A and H3F3B. H3.3 mutant osteosarcomas were
                      re-evaluated in a multidisciplinary manner and analyzed for
                      genome-wide DNA-methylation patterns and DNA copy number
                      aberrations alongside H3.3 wild-type osteosarcomas and H3F3A
                      G34W/L mutant GCTBs.Six osteosarcomas (6/106) carried H3F3A
                      hotspot mutations. No mutations were found in H3F3B. All
                      patients with H3F3A mutant osteosarcoma were older than
                      30 years with a median age of 65 years. Copy number
                      aberrations that are commonly encountered in high-grade
                      osteosarcomas also occurred in H3F3A mutant osteosarcomas.
                      Unlike a single osteosarcoma with a H3F3A K27M mutation, the
                      DNA methylation profiles of H3F3A G34W/R mutant
                      osteosarcomas were clearly different from H3.3 wild-type
                      osteosarcomas, but more closely related to GCTBs. The most
                      differentially methylated promoters between H3F3A G34W/R
                      mutant and H3.3 wild-type osteosarcomas were in KLLN/PTEN
                      (p < 0.00005) and HIST1H2BB (p < 0.0005).H3.3 mutations
                      in osteosarcomas may occur in H3F3A at mutational hotspots.
                      They are overall rare, but become more frequent in
                      osteosarcoma patients older than 30 years. Osteosarcomas
                      carrying H3F3A G34W/R mutations are associated with
                      epigenetic dysregulation of KLLN/PTEN and HIST1H2BB.},
      cin          = {G380 / L101 / B062 / C060 / C010 / W110},
      ddc          = {610},
      cid          = {I:(DE-He78)G380-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)B062-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)C010-20160331 / I:(DE-He78)W110-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28484590},
      pmc          = {pmc:PMC5418758},
      doi          = {10.1186/s13569-017-0075-5},
      url          = {https://inrepo02.dkfz.de/record/131057},
}