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000136812 0247_ $$2ISSN$$a1432-0533
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000136812 1001_ $$0P:(DE-HGF)0$$aSievers, Philipp$$b0$$eFirst author
000136812 245__ $$aFGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma.
000136812 260__ $$aBerlin$$bSpringer$$c2018
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000136812 520__ $$aExtraventricular neurocytoma (EVN) is a rare primary brain tumor occurring in brain parenchyma outside the ventricular system. Histopathological characteristics resemble those of central neurocytoma but exhibit a wider morphologic spectrum. Accurate diagnosis of these histologically heterogeneous tumors is often challenging because of the overlapping morphological features and the lack of defining molecular markers. Here, we explored the molecular landscape of 40 tumors diagnosed histologically as EVN by investigating copy number profiles and DNA methylation array data. DNA methylation profiles were compared with those of relevant differential diagnoses of EVN and with a broader spectrum of diverse brain tumor entities. Based on this, our tumor cohort segregated into different groups. While a large fraction (n = 22) formed a separate epigenetic group clearly distinct from established DNA methylation profiles of other entities, a subset (n = 14) of histologically diagnosed EVN grouped with clusters of other defined entities. Three cases formed a small group close to but separated from the epigenetically distinct EVN cases, and one sample clustered with non-neoplastic brain tissue. Four additional samples originally diagnosed otherwise were found to molecularly resemble EVN. Thus, our results highlight a distinct DNA methylation pattern for the majority of tumors diagnosed as EVN, but also indicate that approximately one third of morphological diagnoses of EVN epigenetically correspond to other brain tumor entities. Copy number analysis and confirmation through RNA sequencing revealed FGFR1-TACC1 fusion as a distinctive, recurrent feature within the EVN methylation group (60%), in addition to a small number of other FGFR rearrangements (13%). In conclusion, our data demonstrate a specific epigenetic signature of EVN suitable for characterization of these tumors as a molecularly distinct entity, and reveal a high frequency of potentially druggable FGFR pathway activation in this tumor group.
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000136812 7001_ $$0P:(DE-He78)d20d08adc992abdb6ccffa1686f1ba17$$aStichel, Damian$$b1
000136812 7001_ $$0P:(DE-He78)e54a1e0999c1d8c95869ef9188b794cc$$aSchrimpf, Daniel$$b2
000136812 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b3
000136812 7001_ $$0P:(DE-HGF)0$$aKoelsche, Christian$$b4
000136812 7001_ $$0P:(DE-HGF)0$$aReuss, David E$$b5
000136812 7001_ $$0P:(DE-HGF)0$$aWefers, Annika K$$b6
000136812 7001_ $$0P:(DE-HGF)0$$aReinhardt, Annekathrin$$b7
000136812 7001_ $$0P:(DE-HGF)0$$aHuang, Kristin$$b8
000136812 7001_ $$0P:(DE-HGF)0$$aEbrahimi, Azadeh$$b9
000136812 7001_ $$aHou, Yanghao$$b10
000136812 7001_ $$0P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d$$aPajtler, Kristian$$b11
000136812 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b12
000136812 7001_ $$aHasselblatt, Martin$$b13
000136812 7001_ $$aStummer, Walter$$b14
000136812 7001_ $$aSchick, Uta$$b15
000136812 7001_ $$aHartmann, Christian$$b16
000136812 7001_ $$aHagel, Christian$$b17
000136812 7001_ $$aStaszewski, Ori$$b18
000136812 7001_ $$0P:(DE-HGF)0$$aReifenberger, Guido$$b19
000136812 7001_ $$aBeschorner, Rudi$$b20
000136812 7001_ $$aCoras, Roland$$b21
000136812 7001_ $$aKeyvani, Kathy$$b22
000136812 7001_ $$aKohlhof, Patricia$$b23
000136812 7001_ $$aDiomedi-Camassei, Francesca$$b24
000136812 7001_ $$aHerold-Mende, Christel$$b25
000136812 7001_ $$aGiangaspero, Felice$$b26
000136812 7001_ $$aRushing, Elisabeth$$b27
000136812 7001_ $$aGiannini, Caterina$$b28
000136812 7001_ $$0P:(DE-He78)8d9c904a6cea14d4c99c78ba46e41f93$$aKorshunov, Andrey$$b29
000136812 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b30$$eLast author
000136812 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b31$$eLast author
000136812 773__ $$0PERI:(DE-600)1458410-4$$a10.1007/s00401-018-1882-3$$gVol. 136, no. 2, p. 293 - 302$$n2$$p293 - 302$$tActa neuropathologica$$v136$$x1432-0533$$y2018
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