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@ARTICLE{Panwalkar:130893,
      author       = {P. Panwalkar and J. Clark and V. Ramaswamy and D. Hawes and
                      F. Yang and C. Dunham and S. Yip and J. Hukin and Y. Sun and
                      M. J. Schipper and L. Chavez$^*$ and A. Margol and M.
                      Pekmezci and C. Chung and A. Banda and J. M. Bayliss and S.
                      J. Curry and M. Santi and F. J. Rodriguez and M. Snuderl and
                      M. A. Karajannis and A. M. Saratsis and C. M. Horbinski and
                      A.-S. Carret and B. Wilson and D. Johnston and L.
                      Lafay-Cousin and S. Zelcer and D. Eisenstat and M. Silva and
                      K. Scheinemann and N. Jabado and P. D. McNeely and M.
                      Kool$^*$ and S. Pfister$^*$ and M. D. Taylor and C. Hawkins
                      and A. Korshunov$^*$ and A. R. Judkins and S. Venneti},
      title        = {{I}mmunohistochemical analysis of {H}3{K}27me3 demonstrates
                      global reduction in group-{A} childhood posterior fossa
                      ependymoma and is a powerful predictor of outcome.},
      journal      = {Acta neuropathologica},
      volume       = {134},
      number       = {5},
      issn         = {1432-0533},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {DKFZ-2017-05969},
      pages        = {705 - 714},
      year         = {2017},
      abstract     = {Posterior fossa ependymomas $(EPN_PF)$ in children comprise
                      two morphologically identical, but biologically distinct
                      tumor entities. Group-A $(EPN_PFA)$ tumors have a poor
                      prognosis and require intensive therapy. In contrast,
                      group-B tumors $(EPN_PFB)$ exhibit excellent prognosis and
                      the current consensus opinion recommends future clinical
                      trials to test the possibility of treatment de-escalation in
                      these patients. Therefore, distinguishing these two tumor
                      subtypes is critical. $EPN_PFA$ and $EPN_PFB$ can be
                      distinguished based on DNA methylation signatures, but these
                      assays are not routinely available. We have previously shown
                      that a subset of poorly prognostic childhood $EPN_PF$
                      exhibits global reduction in H3K27me3. Therefore, we set out
                      to determine whether a simple immunohistochemical assay for
                      H3K27me3 could be used to segregate $EPN_PFA$ from $EPN_PFB$
                      tumors. We assembled a cohort of 230 childhood ependymomas
                      and H3K27me3 immunohistochemistry was assessed as positive
                      or negative in a blinded manner. H3K27me3 staining results
                      were compared with DNA methylation-based subgroup
                      information available in 112 samples $[EPN_PFA$ (n = 72)
                      and $EPN_PFB$ tumors (n = 40)]. H3K27me3 staining was
                      globally reduced in $EPN_PFA$ tumors and
                      immunohistochemistry showed $99\%$ sensitivity and $100\%$
                      specificity in segregating $EPN_PFA$ from $EPN_PFB$ tumors.
                      Moreover, H3K27me3 immunostaining was sufficient to
                      delineate patients with worse prognosis in two independent,
                      non-overlapping cohorts (n = 133 and n = 97). In
                      conclusion, immunohistochemical evaluation of H3K27me3
                      global reduction is an economic, easily available and
                      readily adaptable method for defining high-risk $EPN_PFA$
                      from low-risk posterior fossa $EPN_PFB$ tumors to inform
                      prognosis and to enable the design of future clinical
                      trials.},
      cin          = {B062 / G380 / L101},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)G380-20160331 /
                      I:(DE-He78)L101-20160331},
      pnm          = {319H - Addenda (POF3-319H)},
      pid          = {G:(DE-HGF)POF3-319H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28733933},
      pmc          = {pmc:PMC5647236},
      doi          = {10.1007/s00401-017-1752-4},
      url          = {https://inrepo02.dkfz.de/record/130893},
}