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000168435 037__ $$aDKFZ-2021-00909
000168435 041__ $$aEnglish
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000168435 1001_ $$0P:(DE-He78)c77fccff3e6c42b017b2e8a09813590c$$aSuwala, Abigail Kora$$b0$$eFirst author$$udkfz
000168435 245__ $$aGlioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1.
000168435 260__ $$aHeidelberg$$bSpringer$$c2021
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000168435 500__ $$a#EA:B300#LA:B300# /2021 Jul;142(1):179-189
000168435 520__ $$aGlioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.
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000168435 650_7 $$2Other$$aClassification
000168435 650_7 $$2Other$$aDNA methylation
000168435 650_7 $$2Other$$aGBM
000168435 650_7 $$2Other$$aPNET
000168435 650_7 $$2Other$$aPhenotype
000168435 650_7 $$2Other$$aPlasticity
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000168435 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b2$$udkfz
000168435 7001_ $$aMaas, Sybren L N$$b3
000168435 7001_ $$0P:(DE-He78)45440b44791309bd4b7dbb4f73333f9b$$aSill, Martin$$b4$$udkfz
000168435 7001_ $$aDohmen, Hildegard$$b5
000168435 7001_ $$aBanan, Rouzbeh$$b6
000168435 7001_ $$0P:(DE-He78)856d5c1d0205a79190ed88218ffaf9b2$$aReinhardt, Annekathrin$$b7$$udkfz
000168435 7001_ $$0P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6$$aSievers, Philipp$$b8$$udkfz
000168435 7001_ $$0P:(DE-He78)8126cfb1cc3fa7fa8fd5c20410c6d863$$aHinz, Felix$$b9$$udkfz
000168435 7001_ $$0P:(DE-He78)261d2b84aded878003e6e35d18113831$$aBlattner-Johnson, Mirjam$$b10$$udkfz
000168435 7001_ $$aHartmann, Christian$$b11
000168435 7001_ $$0P:(DE-He78)db2e8cf0dd8fa826896839ffee4b1411$$aSchweizer, Leonille$$b12$$udkfz
000168435 7001_ $$aBoldt, Henning B$$b13
000168435 7001_ $$aKristensen, Bjarne Winther$$b14
000168435 7001_ $$aSchittenhelm, Jens$$b15
000168435 7001_ $$aWood, Matthew D$$b16
000168435 7001_ $$aChotard, Guillaume$$b17
000168435 7001_ $$aBjergvig, Rolf$$b18
000168435 7001_ $$aDas, Anirban$$b19
000168435 7001_ $$aTabori, Uri$$b20
000168435 7001_ $$aHasselblatt, Martin$$b21
000168435 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b22$$udkfz
000168435 7001_ $$aAbdullaev, Zied$$b23
000168435 7001_ $$aQuezado, Martha$$b24
000168435 7001_ $$aAldape, Kenneth$$b25
000168435 7001_ $$0P:(DE-He78)b15b56a6ed37417d476470c60c0140ff$$aHarter, Patrick$$b26
000168435 7001_ $$aSnuderl, Matija$$b27
000168435 7001_ $$aHench, Jürgen$$b28
000168435 7001_ $$aFrank, Stephan$$b29
000168435 7001_ $$aAcker, Till$$b30
000168435 7001_ $$aBrandner, Sebastian$$b31
000168435 7001_ $$0P:(DE-He78)6c294453ee36ad59deddc5494fa6aa4b$$aWinkler, Frank$$b32$$udkfz
000168435 7001_ $$aWesseling, Pieter$$b33
000168435 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan M$$b34$$udkfz
000168435 7001_ $$0P:(DE-He78)d5149ffd74f42a2fa87a086d66645aaa$$aReuss, David E$$b35$$udkfz
000168435 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b36$$udkfz
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000168435 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David T W$$b38$$udkfz
000168435 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b39$$eLast author$$udkfz
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