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@ARTICLE{Katz:141399,
      author       = {L. M. Katz and T. Hielscher$^*$ and B. Liechty and J.
                      Silverman and D. Zagzag and R. Sen and P. Wu and J. G.
                      Golfinos and D. Reuss$^*$ and M. C. Neidert and H.-G.
                      Wirsching and P. Baumgarten and C. Herold-Mende and W.
                      Wick$^*$ and P. Harter$^*$ and M. Weller and A. von
                      Deimling$^*$ and M. Snuderl and C. Sen and F. Sahm$^*$},
      title        = {{L}oss of histone {H}3{K}27me3 identifies a subset of
                      meningiomas with increased risk of recurrence.},
      journal      = {Acta neuropathologica},
      volume       = {135},
      number       = {6},
      issn         = {1432-0533},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2018-01905},
      pages        = {955 - 963},
      year         = {2018},
      abstract     = {Epigenetic patterns on the level of DNA methylation have
                      already been shown to separate clinically relevant
                      subgroups of meningiomas. We here set out to identify
                      potential prognostic implications of epigenetic modification
                      on the level of histones with focus on H3K27 trimethylation
                      (H3K27me3). H3K27me3 was assessed by immunohistochemistry on
                      232 meningiomas from 232 patients. In 194 cases,
                      trimethylation was detected in tumor cells. In 25 cases,
                      staining was limited to vessels while all tumor cells were
                      negative. Finally, 13 cases yielded equivocal staining
                      patterns. Reduced abundance of H3K27me3 in cases with
                      staining limited to vessels was confirmed by mass
                      spectrometry on a subset of cases. Lack of staining for
                      H3K27me3 in all tumor cells was significantly associated
                      with more rapid progression (p = 0.009). In line,
                      H3K27me3-negative cases were associated with a DNA
                      methylation pattern of the more aggressive types among the
                      recently introduced DNA methylation groups. Also, NF2 and
                      SUFU mutations were enriched among cases with complete lack
                      of H3K27me3 staining in tumor cells (p < 0.0001 and
                      p = 0.029, respectively). H3K27me3 staining pattern
                      added significant prognostic insight into WHO grade II cases
                      and in the compound subset of WHO grade I and II cases
                      (p = 0.04 and p = 0.007, respectively). However, it
                      did not further stratify within WHO grade III cases.
                      Collectively, these data indicate that epigenetic
                      modifications beyond DNA methylation are involved in the
                      aggressiveness of meningioma. It also suggests that H3K27me3
                      immunohistochemistry might be a useful adjunct in meningioma
                      diagnostics, particularly for cases with WHO grade II
                      histology or at the borderline between WHO grade I and II.},
      cin          = {C060 / G380 / G370 / L501 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)G370-20160331 / I:(DE-He78)L501-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29627952},
      doi          = {10.1007/s00401-018-1844-9},
      url          = {https://inrepo02.dkfz.de/record/141399},
}