TY  - JOUR
AU  - Koelsche, Christian
AU  - Kriegsmann, Mark
AU  - Kommoss, Felix K F
AU  - Stichel, Damian
AU  - Kriegsmann, Katharina
AU  - Vokuhl, Christian
AU  - Grünewald, Thomas G P
AU  - Romero-Pérez, Laura
AU  - Kirchner, Thomas
AU  - de Alava, Enrique
AU  - Diaz-Martin, Juan
AU  - Hartmann, Wolfgang
AU  - Baumhoer, Daniel
AU  - Antonescu, Cristina R
AU  - Szuhai, Karoly
AU  - Flucke, Uta
AU  - Dirksen, Uta
AU  - Pfister, Stefan
AU  - Jones, David
AU  - Mechtersheimer, Gunhild
AU  - von Deimling, Andreas
TI  - DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma.
JO  - Journal of cancer research and clinical oncology
VL  - 145
IS  - 5
SN  - 0171-5216
CY  - Berlin
PB  - Springer42162
M1  - DKFZ-2019-00946
SP  - 1273-1281
PY  - 2019
N1  - 145(5):1273-1281
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30895378
DO  - DOI:10.1007/s00432-019-02895-2
UR  - https://inrepo02.dkfz.de/record/143358
ER  -