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000143358 1001_ $$00000-0001-8763-8864$$aKoelsche, Christian$$b0
000143358 245__ $$aDNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma.
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000143358 520__ $$aRecent studies revealed divergent gene expression patterns in Ewing sarcoma (EwS) with canonical EWSR1-ETS gene fusions and undifferentiated round cell sarcomas (URCS) with EWSR1 rearrangements fused to the non-ETS gene NFATc2. Thus, the question arises whether the latter tumors really belong to EwS.We collected five cases matching the group of URCS with EWSR1-NFATc2 fusion and performed DNA methylation and copy number profiling. Results were compared to methylation data of 30 EwS with various EWSR1-ETS fusions and one EwS with FUS-ERG fusion, 16 URCS with CIC rearrangement and 10 URCS with BCOR alteration and a total of 81 EWSR1-associated soft tissue sarcomas including 7 angiomatoid fibrous histiocytomas, 7 clear cell sarcomas of the soft tissue, 28 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondrosarcomas and 29 myxoid liposarcomas.Unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analysis of DNA methylation data revealed a homogeneous methylation cluster for URCS with EWSR1-NFATc2 fusion, which clearly segregated from EwS and the other subtypes. Copy number profiles of EWSR1-NFATc2 cases showed recurrent losses on chromosome 9q and segmental gains on 20q13 and 22q12 involving the EWSR1 and NFATc2 loci, respectively.In summary, URCS with EWSR1-NFATc2 fusion share a distinct DNA methylation signature and carry characteristic copy number alterations, which emphasizes that these sarcomas should be considered separately from EwS.
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000143358 7001_ $$aVokuhl, Christian$$b5
000143358 7001_ $$0P:(DE-HGF)0$$aGrünewald, Thomas G P$$b6
000143358 7001_ $$aRomero-Pérez, Laura$$b7
000143358 7001_ $$0P:(DE-He78)fd68f49dada874ac262fadf9fde869df$$aKirchner, Thomas$$b8$$udkfz
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000143358 7001_ $$aDiaz-Martin, Juan$$b10
000143358 7001_ $$aHartmann, Wolfgang$$b11
000143358 7001_ $$aBaumhoer, Daniel$$b12
000143358 7001_ $$aAntonescu, Cristina R$$b13
000143358 7001_ $$aSzuhai, Karoly$$b14
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000143358 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b17$$udkfz
000143358 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b18$$udkfz
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