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000130893 1001_ $$aPanwalkar, Pooja$$b0
000130893 245__ $$aImmunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.
000130893 260__ $$aBerlin$$bSpringer$$c2017
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000130893 520__ $$aPosterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.
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000130893 7001_ $$aClark, Jonathan$$b1
000130893 7001_ $$aRamaswamy, Vijay$$b2
000130893 7001_ $$aHawes, Debra$$b3
000130893 7001_ $$aYang, Fusheng$$b4
000130893 7001_ $$aDunham, Christopher$$b5
000130893 7001_ $$aYip, Stephen$$b6
000130893 7001_ $$aHukin, Juliette$$b7
000130893 7001_ $$aSun, Yilun$$b8
000130893 7001_ $$aSchipper, Matthew J$$b9
000130893 7001_ $$0P:(DE-He78)082dd3179733e3e716a58eb90f418a78$$aChavez, Lukas$$b10$$udkfz
000130893 7001_ $$aMargol, Ashley$$b11
000130893 7001_ $$aPekmezci, Melike$$b12
000130893 7001_ $$aChung, Chan$$b13
000130893 7001_ $$aBanda, Adam$$b14
000130893 7001_ $$aBayliss, Jill M$$b15
000130893 7001_ $$aCurry, Sarah J$$b16
000130893 7001_ $$aSanti, Mariarita$$b17
000130893 7001_ $$aRodriguez, Fausto J$$b18
000130893 7001_ $$aSnuderl, Matija$$b19
000130893 7001_ $$aKarajannis, Matthias A$$b20
000130893 7001_ $$aSaratsis, Amanda M$$b21
000130893 7001_ $$aHorbinski, Craig M$$b22
000130893 7001_ $$aCarret, Anne-Sophie$$b23
000130893 7001_ $$aWilson, Beverly$$b24
000130893 7001_ $$aJohnston, Donna$$b25
000130893 7001_ $$aLafay-Cousin, Lucie$$b26
000130893 7001_ $$aZelcer, Shayna$$b27
000130893 7001_ $$aEisenstat, David$$b28
000130893 7001_ $$aSilva, Marianna$$b29
000130893 7001_ $$aScheinemann, Katrin$$b30
000130893 7001_ $$aJabado, Nada$$b31
000130893 7001_ $$aMcNeely, P Daniel$$b32
000130893 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b33$$udkfz
000130893 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b34$$udkfz
000130893 7001_ $$aTaylor, Michael D$$b35
000130893 7001_ $$aHawkins, Cynthia$$b36
000130893 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b37$$udkfz
000130893 7001_ $$aJudkins, Alexander R$$b38
000130893 7001_ $$aVenneti, Sriram$$b39
000130893 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-017-1752-4$$gVol. 134, no. 5, p. 705 - 714$$n5$$p705 - 714$$tActa neuropathologica$$v134$$x1432-0533$$y2017
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