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000178456 1001_ $$0P:(DE-He78)c1e6f8388afe92ba3e13be35e7bf54d8$$aEbrahimi, Azadeh$$b0$$eFirst author$$udkfz
000178456 245__ $$aPleomorphic xanthoastrocytoma is a heterogeneous entity with pTERT mutations prognosticating shorter survival.
000178456 260__ $$aLondon$$bBiomed Central$$c2022
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000178456 520__ $$aPleomorphic xanthoastrocytoma (PXA) in its classic manifestation exhibits distinct morphological features and is assigned to CNS WHO grade 2 or grade 3. Distinction from glioblastoma variants and lower grade glial and glioneuronal tumors is a common diagnostic challenge. We compared a morphologically defined set of PXA (histPXA) with an independent set, defined by DNA methylation analysis (mcPXA). HistPXA encompassed 144 tumors all subjected to DNA methylation array analysis. Sixty-two histPXA matched to the methylation class mcPXA. These were combined with the cases that showed the mcPXA signature but had received a histopathological diagnosis other than PXA. This cohort constituted a set of 220 mcPXA. Molecular and clinical parameters were analyzed in these groups. Morphological parameters were analyzed in a subset of tumors with FFPE tissue available. HistPXA revealed considerable heterogeneity in regard to methylation classes, with methylation classes glioblastoma and ganglioglioma being the most frequent mismatches. Similarly, the mcPXA cohort contained tumors of diverse histological diagnoses, with glioblastoma constituting the most frequent mismatch. Subsequent analyses demonstrated the presence of canonical pTERT mutations to be associated with unfavorable prognosis among mcPXA. Based on these data, we consider the tumor type PXA to be histologically more varied than previously assumed. Histological approach to diagnosis will predominantly identify cases with the established archetypical morphology. DNA methylation analysis includes additional tumors in the tumor class PXA that share similar DNA methylation profile but lack the typical morphology of a PXA. DNA methylation analysis also assist in separating other tumor types with morphologic overlap to PXA. Our data suggest the presence of canonical pTERT mutations as a robust indicator for poor prognosis in methylation class PXA.
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000178456 650_7 $$2Other$$aBRAF V600E
000178456 650_7 $$2Other$$aDNA methylation array profiling
000178456 650_7 $$2Other$$aEpithelioid glioblastoma
000178456 650_7 $$2Other$$aGanglioglioma
000178456 650_7 $$2Other$$aPleomorphic xanthoastrocytoma
000178456 650_7 $$2Other$$apTERT mutation
000178456 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b1$$udkfz
000178456 7001_ $$0P:(DE-HGF)0$$aReifenberger, Guido$$b2
000178456 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b3$$udkfz
000178456 7001_ $$aFelsberg, Joerg$$b4
000178456 7001_ $$aTrisolini, Elena$$b5
000178456 7001_ $$aPollo, Bianca$$b6
000178456 7001_ $$aCalatozzolo, Chiara$$b7
000178456 7001_ $$aPrinz, Marco$$b8
000178456 7001_ $$aStaszewski, Ori$$b9
000178456 7001_ $$aSchweizer, Leonille$$b10
000178456 7001_ $$aSchittenhelm, Jens$$b11
000178456 7001_ $$0P:(DE-He78)b15b56a6ed37417d476470c60c0140ff$$aHarter, Patrick$$b12
000178456 7001_ $$aPaulus, Werner$$b13
000178456 7001_ $$aThomas, Christian$$b14
000178456 7001_ $$aKohlhof-Meinecke, Patricia$$b15
000178456 7001_ $$aSeiz-Rosenhagen, Marcel$$b16
000178456 7001_ $$0P:(DE-He78)0be2f86573954f87e97f8a4dbb05cb0f$$aMilde, Till$$b17$$udkfz
000178456 7001_ $$0P:(DE-He78)1e5010244cbd57412baa2f0e2806a182$$aCasalini, Maria Belen$$b18
000178456 7001_ $$0P:(DE-He78)c77fccff3e6c42b017b2e8a09813590c$$aSuwala, Abigail$$b19$$udkfz
000178456 7001_ $$0P:(DE-He78)32977c5abc127b0373ece54294a41f63$$aWefers, Annika K$$b20$$udkfz
000178456 7001_ $$0P:(DE-He78)856d5c1d0205a79190ed88218ffaf9b2$$aReinhardt, Annekathrin$$b21$$udkfz
000178456 7001_ $$0P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6$$aSievers, Philipp$$b22$$udkfz
000178456 7001_ $$aKramm, Christof M$$b23
000178456 7001_ $$aEtminam, Nima$$b24
000178456 7001_ $$aUnterberg, Andreas$$b25
000178456 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b26$$udkfz
000178456 7001_ $$aHerold-Mende, Christel$$b27
000178456 7001_ $$0P:(DE-He78)a46a5b2a871859c8e2d63d2f8c666807$$aSturm, Dominik$$b28$$udkfz
000178456 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b29$$udkfz
000178456 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b30$$udkfz
000178456 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b31$$udkfz
000178456 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b32$$udkfz
000178456 7001_ $$0P:(DE-He78)d5149ffd74f42a2fa87a086d66645aaa$$aReuss, David E$$b33$$udkfz
000178456 7001_ $$aAldape, Ken$$b34
000178456 7001_ $$aAbdullaev, Zied$$b35
000178456 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b36$$udkfz
000178456 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b37$$udkfz
000178456 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b38$$eLast author$$udkfz
000178456 773__ $$0PERI:(DE-600)2715589-4$$a10.1186/s40478-021-01308-1$$gVol. 10, no. 1, p. 5$$n1$$p5$$tActa Neuropathologica Communications$$v10$$x2051-5960$$y2022
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