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000147249 1001_ $$0P:(DE-He78)32977c5abc127b0373ece54294a41f63$$aWefers, Annika$$b0$$eFirst author
000147249 245__ $$aIsomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course.
000147249 260__ $$aHeidelberg$$bSpringer$$c2020
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000147249 500__ $$a2020 Jan;139(1):193-209#EA:B300#
000147249 520__ $$aThe 'isomorphic subtype of diffuse astrocytoma' was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification.
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000147249 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b1
000147249 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b2
000147249 7001_ $$aCoras, Roland$$b3
000147249 7001_ $$aPages, Mélanie$$b4
000147249 7001_ $$aTauziède-Espariat, Arnault$$b5
000147249 7001_ $$aVarlet, Pascale$$b6
000147249 7001_ $$0P:(DE-He78)a46ef05266eafb5f42c207880f97ebf6$$aSchwarz, Daniel$$b7
000147249 7001_ $$aSöylemezoglu, Figen$$b8
000147249 7001_ $$aPohl, Ute$$b9
000147249 7001_ $$aPimentel, José$$b10
000147249 7001_ $$0P:(DE-He78)b6273c0ba3ae37a4d3d1c6b084797f2e$$aMeyer, Jochen$$b11
000147249 7001_ $$aHewer, Ekkehard$$b12
000147249 7001_ $$aJapp, Anna$$b13
000147249 7001_ $$aJoshi, Abhijit$$b14
000147249 7001_ $$0P:(DE-HGF)0$$aReuss, David E$$b15
000147249 7001_ $$0P:(DE-He78)856d5c1d0205a79190ed88218ffaf9b2$$aReinhardt, Annekathrin$$b16
000147249 7001_ $$0P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6$$aSievers, Philipp$$b17
000147249 7001_ $$0P:(DE-He78)1e5010244cbd57412baa2f0e2806a182$$aCasalini, Maria Belen$$b18
000147249 7001_ $$0P:(DE-He78)c1e6f8388afe92ba3e13be35e7bf54d8$$aEbrahimi, Azadeh$$b19
000147249 7001_ $$0P:(DE-HGF)0$$aHuang, Kristin$$b20
000147249 7001_ $$aKoelsche, Christian$$b21
000147249 7001_ $$aLow, Hu Liang$$b22
000147249 7001_ $$aRebelo, Olinda$$b23
000147249 7001_ $$aMarnoto, Dina$$b24
000147249 7001_ $$aBecker, Albert J$$b25
000147249 7001_ $$aStaszewski, Ori$$b26
000147249 7001_ $$aMittelbronn, Michel$$b27
000147249 7001_ $$aHasselblatt, Martin$$b28
000147249 7001_ $$aSchittenhelm, Jens$$b29
000147249 7001_ $$aCheesman, Edmund$$b30
000147249 7001_ $$ade Oliveira, Ricardo Santos$$b31
000147249 7001_ $$aQueiroz, Rosane Gomes P$$b32
000147249 7001_ $$aValera, Elvis Terci$$b33
000147249 7001_ $$aHans, Volkmar H$$b34
000147249 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b35
000147249 7001_ $$aOlar, Adriana$$b36
000147249 7001_ $$aLigon, Keith L$$b37
000147249 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b38
000147249 7001_ $$aJaunmuktane, Zane$$b39
000147249 7001_ $$aBrandner, Sebastian$$b40
000147249 7001_ $$aTatevossian, Ruth G$$b41
000147249 7001_ $$aEllison, David W$$b42
000147249 7001_ $$aJacques, Thomas S$$b43
000147249 7001_ $$aHonavar, Mrinalini$$b44
000147249 7001_ $$aAronica, Eleonora$$b45
000147249 7001_ $$aThom, Maria$$b46
000147249 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b47
000147249 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b48
000147249 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b49
000147249 7001_ $$aBlumcke, Ingmar$$b50
000147249 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b51
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