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: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 March 2019
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| 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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| 245 | 1 | 0 | |a DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1-NFATc2 fusion from Ewing sarcoma |c 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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| 520 | |a 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. | ||
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