Erschienen in:
20.03.2019 | Original Article – Cancer Research
DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1–NFATc2 fusion from Ewing sarcoma
verfasst von:
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
Erschienen in:
Journal of Cancer Research and Clinical Oncology
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Ausgabe 5/2019
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Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.