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DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma

PurposeRecent 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...

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Main Authors: Kölsche, Christian (Author) , Kriegsmann, Mark (Author) , Kommoss, Felix (Author) , Stichel, Damian (Author) , Pfister, Stefan (Author) , Jones, David T. W. (Author) , Mechtersheimer, Gunhild (Author) , Deimling, Andreas von (Author)
Format: Article (Journal)
Language:English
Published: 20 March 2019
In: Journal of cancer research and clinical oncology
Year: 2019, Volume: 145, Issue: 5, Pages: 1273-1281
ISSN:1432-1335
DOI:10.1007/s00432-019-02895-2
Online Access:Verlag, Volltext: https://doi.org/10.1007/s00432-019-02895-2
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Author Notes:Christian Koelsche, Mark Kriegsmann, Felix K. F. Kommoss, Damian Stichel, Katharina Kriegsmann, Christian Vokuhl, Thomas G. P. Grünewald, Laura Romero-Pérez, Thomas Kirchner, Enrique de Alava, Juan Diaz-Martin, Wolfgang Hartmann, Daniel Baumhoer, Cristina R. Antonescu, Karoly Szuhai, Uta Flucke, Uta Dirksen, Stefan M. Pfister, David T. W. Jones, Gunhild Mechtersheimer, Andreas von Deimling
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Summary:PurposeRecent 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.MethodsWe 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.ResultsUnsupervised 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.ConclusionIn 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.
Item Description:Gesehen am 04.07.2019
Physical Description:Online Resource
ISSN:1432-1335
DOI:10.1007/s00432-019-02895-2

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