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000127371 1001_ $$0P:(DE-HGF)0$$aReuss, David E$$b0$$eFirst author
000127371 245__ $$aAdult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities.
000127371 260__ $$aBerlin$$bSpringer$$c2015
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000127371 520__ $$aIDH wild type (IDHwt) anaplastic astrocytomas WHO grade III (AA III) are associated with poor outcome. To address the possibilities of molecular subsets among astrocytoma or of diagnostic reclassification, we analyzed a series of 160 adult IDHwt tumors comprising 120 AA III and 40 diffuse astrocytomas WHO grade II (A II) for molecular hallmark alterations and established methylation and copy number profiles. Based on molecular profiles and hallmark alterations the tumors could be grouped into four major sets. 124/160 (78 %) tumors were diagnosed as the molecular equivalent of conventional glioblastoma (GBM), and 15/160 (9 %) as GBM-H3F3A mutated (GBM-H3). 13/160 (8 %) exhibited a distinct methylation profile that was most similar to GBM-H3-K27, however, lacked the H3F3A mutation. This group was enriched for tumors of infratentorial and midline localization and showed a trend towards a more favorable prognosis. All but one of the 120 IDHwt AA III could be assigned to these three groups. 7 tumors recruited from the 40 A II, comprised a variety of molecular signatures and all but one were reclassified into distinct WHO entities of lower grades. Interestingly, TERT mutations were exclusively restricted to the molecular GBM (78 %) and associated with poor clinical outcome. However, the GBM-H3 group lacking TERT mutations appeared to fare even worse. Our data demonstrate that most of the tumors diagnosed as IDHwt astrocytomas can be allocated to other tumor entities on a molecular basis. The diagnosis of IDHwt diffuse astrocytoma or anaplastic astrocytoma should be used with caution.
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000127371 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000127371 650_7 $$0EC 1.1.1.41$$2NLM Chemicals$$aIsocitrate Dehydrogenase
000127371 650_7 $$0EC 1.1.1.41$$2NLM Chemicals$$aisocitrate dehydrogenase 2, human
000127371 650_7 $$0EC 1.1.1.42.$$2NLM Chemicals$$aIDH1 protein, human
000127371 650_7 $$0EC 2.7.7.49$$2NLM Chemicals$$aTERT protein, human
000127371 650_7 $$0EC 2.7.7.49$$2NLM Chemicals$$aTelomerase
000127371 7001_ $$0P:(DE-HGF)0$$aKratz, Annekathrin$$b1
000127371 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b2$$udkfz
000127371 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b3$$udkfz
000127371 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b4$$udkfz
000127371 7001_ $$0P:(DE-HGF)0$$aKoelsche, Christian$$b5
000127371 7001_ $$0P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aHovestadt, Volker$$b6$$udkfz
000127371 7001_ $$0P:(DE-He78)7999346780553d7fab7ba69d5afdfa71$$aBewerunge-Hudler, Melanie$$b7$$udkfz
000127371 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b8$$udkfz
000127371 7001_ $$aSchittenhelm, Jens$$b9
000127371 7001_ $$0P:(DE-He78)3494efbbc54460b109fe9eab0595adda$$aMittelbronn, Michel$$b10$$udkfz
000127371 7001_ $$aRushing, Elisabeth$$b11
000127371 7001_ $$aSimon, Matthias$$b12
000127371 7001_ $$aWestphal, Manfred$$b13
000127371 7001_ $$aUnterberg, Andreas$$b14
000127371 7001_ $$0P:(DE-He78)5ef8651b0f857b9c640aa5b1498c43b5$$aPlatten, Michael$$b15$$udkfz
000127371 7001_ $$aPaulus, Werner$$b16
000127371 7001_ $$0P:(DE-HGF)0$$aReifenberger, Guido$$b17
000127371 7001_ $$aTonn, Joerg-Christian$$b18
000127371 7001_ $$aAldape, Kenneth$$b19
000127371 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b20$$udkfz
000127371 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b21$$udkfz
000127371 7001_ $$aWeller, Michael$$b22
000127371 7001_ $$aHerold-Mende, Christel$$b23
000127371 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b24$$udkfz
000127371 7001_ $$aBrandner, Sebastian$$b25
000127371 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b26$$eLast author$$udkfz
000127371 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-015-1454-8$$gVol. 130, no. 3, p. 407 - 417$$n3$$p407 - 417$$tActa neuropathologica$$v130$$x1432-0533$$y2015
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