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000126577 1001_ $$aGeisenberger, Christoph$$b0
000126577 245__ $$aMolecular profiling of long-term survivors identifies a subgroup of glioblastoma characterized by chromosome 19/20 co-gain.
000126577 260__ $$aBerlin$$bSpringer$$c2015
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000126577 520__ $$aGlioblastoma (GBM) is a devastating tumor and few patients survive beyond 3 years. Defining the molecular determinants underlying long-term survival is essential for insights into tumor biology and biomarker identification. We therefore investigated homogeneously treated, IDH (wt) long-term (LTS, n = 10) and short-term survivors (STS, n = 6) by microarray transcription profiling. While there was no association of clinical parameters and molecular subtypes with long-term survival, STS tumors were characterized by differential polarization of infiltrating microglia with predominance of the M2 phenotype detectable both on the mRNA and protein level. Furthermore, transcriptional signatures of LTS and STS predicted patient outcome in a large, IDH (wt) cohort (n = 468). Interrogation of overlapping genomic alterations identified concurrent gain of chromosomes 19 and 20 as a favorable prognostic marker. The strong association of this co-gain with survival was validated by aCGH in a second, independent cohort (n = 124). Finally, FISH and gene expression data revealed gains to constitute low-amplitude, clonal events with a strong impact on transcription. In conclusion, these findings provide important insights into the manipulation of the innate immune system by particularly aggressive GBM tumors. Furthermore, we genomically characterize a previously unknown, clinically relevant subgroup of glioblastoma, which can easily be identified through modern neuropathological workup.
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000126577 650_7 $$2NLM Chemicals$$aRNA, Messenger
000126577 650_7 $$0EC 1.1.1.41$$2NLM Chemicals$$aIsocitrate Dehydrogenase
000126577 650_7 $$0EC 1.1.1.42.$$2NLM Chemicals$$aIDH1 protein, human
000126577 7001_ $$0P:(DE-HGF)0$$aMock, Andreas$$b1
000126577 7001_ $$aWarta, Rolf$$b2
000126577 7001_ $$aRapp, Carmen$$b3
000126577 7001_ $$0P:(DE-He78)660cb858f5b7062b4ef81f3273372139$$aSchwager, Christian$$b4$$udkfz
000126577 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b5$$udkfz
000126577 7001_ $$aNied, Ann-Katrin$$b6
000126577 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b7$$udkfz
000126577 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b8$$udkfz
000126577 7001_ $$aJungk, Christine$$b9
000126577 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b10$$udkfz
000126577 7001_ $$aCollins, V Peter$$b11
000126577 7001_ $$aIchimura, Koichi$$b12
000126577 7001_ $$aBäcklund, L Magnus$$b13
000126577 7001_ $$0P:(DE-He78)892d1e8f0e9745ab53a84d41f77e87ca$$aSchnabel, Elena$$b14$$udkfz
000126577 7001_ $$aMittelbron, Michel$$b15
000126577 7001_ $$aLahrmann, Bernd$$b16
000126577 7001_ $$aZheng, Siyuan$$b17
000126577 7001_ $$aVerhaak, Roel G W$$b18
000126577 7001_ $$aGrabe, Niels$$b19
000126577 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b20$$udkfz
000126577 7001_ $$aHartmann, Christian$$b21
000126577 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b22$$udkfz
000126577 7001_ $$aDebus, Jürgen$$b23
000126577 7001_ $$aUnterberg, Andreas$$b24
000126577 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b25$$udkfz
000126577 7001_ $$aHerold-Mende, Christel$$b26
000126577 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-015-1427-y$$gVol. 130, no. 3, p. 419 - 434$$n3$$p419 - 434$$tActa neuropathologica$$v130$$x1432-0533$$y2015
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