%0 Journal Article
%A Koelsche, Christian
%A Kriegsmann, Mark
%A Kommoss, Felix K F
%A Stichel, Damian
%A Kriegsmann, Katharina
%A Vokuhl, Christian
%A Grünewald, Thomas G P
%A Romero-Perez, Laura
%A Kirchner, Thomas
%A de Alava, Enrique
%A Diaz-Martin, Juan
%A Hartmann, Wolfgang
%A Baumhoer, Daniel
%A Antonescu, Cristina R
%A Szuhai, Karoly
%A Flucke, Uta
%A Dirksen, Uta
%A Pfister, Stefan M
%A Jones, David T W
%A Mechtersheimer, Gunhild
%A von Deimling, Andreas
%T DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma.
%D 2019
%U http://hdl.handle.net/10668/13741
%X Recent 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.
%K DNA methylation
%K EWSR1
%K Ewing
%K Ewing like
%K NFATc2
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