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000136789 1001_ $$0P:(DE-HGF)0$$aReinhardt, Annekathrin$$b0$$eFirst author
000136789 245__ $$aAnaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations.
000136789 260__ $$aBerlin$$bSpringer$$c2018
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000136789 520__ $$aTumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas. T-distributed stochastic neighbor-embedding (t-SNE) and hierarchical clustering analysis of these 102 cases against 158 reference cases from 12 glioma reference classes revealed that a subset of 83 of these tumors share a common DNA methylation profile that is distinct from the reference classes. These 83 tumors were thus denominated DNA methylation class anaplastic astrocytoma with piloid features (MC AAP). The 19 remaining tumors were distributed amongst the reference classes, with additional testing confirming the molecular diagnosis in most cases. Median age of patients with MC AAP was 41.5 years. The most frequent localization was the posterior fossa (74%). Deletions of CDKN2A/B (66/83, 80%), MAPK pathway gene alterations (49/65, 75%, most frequently affecting NF1, followed by BRAF and FGFR1) and mutations of ATRX or loss of ATRX expression (33/74, 45%) were the most common molecular alterations. All tumors were IDH1/2 wildtype. The MGMT promoter was methylated in 38/83 tumors (45%). Outcome analysis confirmed an unfavorable clinical course in comparison to PA, but better than IDH wildtype glioblastoma. In conclusion, we show that a subset of histologically defined anaplastic pilocytic astrocytomas forms a separate DNA methylation cluster, harbors recurrent alterations in MAPK pathway genes in combination with alterations of CDKN2A/B and ATRX, affects patients who are on average older than those diagnosed with PA and has an intermediate clinical outcome.
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000136789 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b2
000136789 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b3
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000136789 7001_ $$0P:(DE-HGF)0$$aReuss, David E$$b5
000136789 7001_ $$0P:(DE-HGF)0$$aKoelsche, Christian$$b6
000136789 7001_ $$0P:(DE-HGF)0$$aHuang, Kristin$$b7
000136789 7001_ $$0P:(DE-HGF)0$$aWefers, Annika K$$b8
000136789 7001_ $$0P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aHovestadt, Volker$$b9
000136789 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b10
000136789 7001_ $$aGramatzki, Dorothee$$b11
000136789 7001_ $$aFelsberg, Joerg$$b12
000136789 7001_ $$aReifenberger, Guido$$b13
000136789 7001_ $$aKoch, Arend$$b14
000136789 7001_ $$aThomale, Ulrich-W$$b15
000136789 7001_ $$aBecker, Albert$$b16
000136789 7001_ $$aHans, Volkmar H$$b17
000136789 7001_ $$aPrinz, Marco$$b18
000136789 7001_ $$aStaszewski, Ori$$b19
000136789 7001_ $$aAcker, Till$$b20
000136789 7001_ $$aDohmen, Hildegard$$b21
000136789 7001_ $$aHartmann, Christian$$b22
000136789 7001_ $$aMueller, Wolf$$b23
000136789 7001_ $$aTuffaha, Muin S A$$b24
000136789 7001_ $$aPaulus, Werner$$b25
000136789 7001_ $$aHeß, Katharina$$b26
000136789 7001_ $$aBrokinkel, Benjamin$$b27
000136789 7001_ $$aSchittenhelm, Jens$$b28
000136789 7001_ $$aMonoranu, Camelia-Maria$$b29
000136789 7001_ $$aKessler, Almuth Friederike$$b30
000136789 7001_ $$aLoehr, Mario$$b31
000136789 7001_ $$aBuslei, Rolf$$b32
000136789 7001_ $$aDeckert, Martina$$b33
000136789 7001_ $$aMawrin, Christian$$b34
000136789 7001_ $$aKohlhof, Patricia$$b35
000136789 7001_ $$aHewer, Ekkehard$$b36
000136789 7001_ $$aOlar, Adriana$$b37
000136789 7001_ $$aRodriguez, Fausto J$$b38
000136789 7001_ $$aGiannini, Caterina$$b39
000136789 7001_ $$aNageswaraRao, Amulya A$$b40
000136789 7001_ $$aTabori, Uri$$b41
000136789 7001_ $$aNunes, Nuno Miguel$$b42
000136789 7001_ $$aWeller, Michael$$b43
000136789 7001_ $$aPohl, Ute$$b44
000136789 7001_ $$aJaunmuktane, Zane$$b45
000136789 7001_ $$aBrandner, Sebastian$$b46
000136789 7001_ $$aUnterberg, Andreas$$b47
000136789 7001_ $$aHänggi, Daniel$$b48
000136789 7001_ $$0P:(DE-He78)5ef8651b0f857b9c640aa5b1498c43b5$$aPlatten, Michael$$b49
000136789 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b50
000136789 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b51
000136789 7001_ $$aHerold-Mende, Christel$$b52
000136789 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b53$$eLast author
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000136789 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b55$$eLast author
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