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@ARTICLE{Bechet:119629,
      author       = {D. Bechet and G. G. H. Gielen and A. Korshunov$^*$ and S.
                      Pfister$^*$ and C. Rousso and D. Faury and P.-O. Fiset and
                      N. Benlimane and P. W. Lewis and C. Lu and C. David Allis
                      and M. W. Kieran and K. L. Ligon and T. Pietsch and B.
                      Ellezam and S. Albrecht and N. Jabado},
      title        = {{S}pecific detection of methionine 27 mutation in histone 3
                      variants ({H}3{K}27{M}) in fixed tissue from high-grade
                      astrocytomas.},
      journal      = {Acta neuropathologica},
      volume       = {128},
      number       = {5},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-00260},
      pages        = {733 - 741},
      year         = {2014},
      abstract     = {Studies in pediatric high-grade astrocytomas (HGA) by our
                      group and others have uncovered recurrent somatic mutations
                      affecting highly conserved residues in histone 3 (H3)
                      variants. One of these mutations leads to analogous
                      p.Lys27Met (K27M) mutations in both H3.3 and H3.1 variants,
                      is associated with rapid fatal outcome, and occurs
                      specifically in HGA of the midline in children and young
                      adults. This includes diffuse intrinsic pontine gliomas
                      $(80 \%)$ and thalamic or spinal HGA $(>90 \%),$ which are
                      surgically challenging locations with often limited tumor
                      material available and critical need for specific
                      histopathological markers. Here, we analyzed formalin-fixed
                      paraffin-embedded tissues from 143 pediatric HGA and 297
                      other primary brain tumors or normal brain.
                      Immunohistochemical staining for H3K27M was compared to
                      tumor genotype, and also compared to H3 tri-methylated
                      lysine 27 (H3K27me3) staining, previously shown to be
                      drastically decreased in samples carrying this mutation.
                      There was a $100 \%$ concordance between genotype and
                      immunohistochemical analysis of H3K27M in tumor samples.
                      Mutant H3K27M was expressed in the majority of tumor cells,
                      indicating limited intra-tumor heterogeneity for this
                      specific mutation within the limits of our dataset. Both
                      H3.1 and H3.3K27M mutants were recognized by this antibody
                      while non-neoplastic elements, such as endothelial and
                      vascular smooth muscle cells or lymphocytes, did not stain.
                      H3K27me3 immunoreactivity was largely mutually exclusive
                      with H3K27M positivity. These results demonstrate that
                      mutant H3K27M can be specifically identified with high
                      specificity and sensitivity using an H3K27M antibody and
                      immunohistochemistry. Use of this antibody in the clinical
                      setting will prove very useful for diagnosis, especially in
                      the context of small biopsies in challenging midline tumors
                      and will help orient care in the context of the extremely
                      poor prognosis associated with this mutation.},
      keywords     = {Histones (NLM Chemicals) / Methionine (NLM Chemicals)},
      cin          = {G380 / B062},
      ddc          = {610},
      cid          = {I:(DE-He78)G380-20160331 / I:(DE-He78)B062-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25200321},
      pmc          = {pmc:PMC4201745},
      doi          = {10.1007/s00401-014-1337-4},
      url          = {https://inrepo02.dkfz.de/record/119629},
}