TY - JOUR
AU - Panwalkar, Pooja
AU - Clark, Jonathan
AU - Ramaswamy, Vijay
AU - Hawes, Debra
AU - Yang, Fusheng
AU - Dunham, Christopher
AU - Yip, Stephen
AU - Hukin, Juliette
AU - Sun, Yilun
AU - Schipper, Matthew J
AU - Chavez, Lukas
AU - Margol, Ashley
AU - Pekmezci, Melike
AU - Chung, Chan
AU - Banda, Adam
AU - Bayliss, Jill M
AU - Curry, Sarah J
AU - Santi, Mariarita
AU - Rodriguez, Fausto J
AU - Snuderl, Matija
AU - Karajannis, Matthias A
AU - Saratsis, Amanda M
AU - Horbinski, Craig M
AU - Carret, Anne-Sophie
AU - Wilson, Beverly
AU - Johnston, Donna
AU - Lafay-Cousin, Lucie
AU - Zelcer, Shayna
AU - Eisenstat, David
AU - Silva, Marianna
AU - Scheinemann, Katrin
AU - Jabado, Nada
AU - McNeely, P Daniel
AU - Kool, Marcel
AU - Pfister, Stefan
AU - Taylor, Michael D
AU - Hawkins, Cynthia
AU - Korshunov, Andrey
AU - Judkins, Alexander R
AU - Venneti, Sriram
TI - Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.
JO - Acta neuropathologica
VL - 134
IS - 5
SN - 1432-0533
CY - Berlin
PB - Springer
M1 - DKFZ-2017-05969
SP - 705 - 714
PY - 2017
AB - 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
LB - PUB:(DE-HGF)16
C6 - pmid:28733933
C2 - pmc:PMC5647236
DO - DOI:10.1007/s00401-017-1752-4
UR - https://inrepo02.dkfz.de/record/130893
ER -