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MCR-21-0354_SF5 from Identification of a Novel FUS/ETV4 Fusion and Comparative Analysis with Other Ewing Sarcoma Fusion Proteins

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posted on 2023-08-08, 17:20 authored by Megann A. Boone, Cenny Taslim, Jesse C. Crow, Julia Selich-Anderson, Mike Watson, Peter Heppner, James Hamill, Andrew C. Wood, Stephen L. Lessnick, Mark Winstanley

Supp Figure 5 demonstrates similar DNA-binding patterns between FET/ETS proteins at EWS/FLI-specific regulatory elements.

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National Institutes of Health (NIH)

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ARTICLE ABSTRACT

Ewing sarcoma is a pediatric bone cancer defined by a chromosomal translocation fusing one of the FET family members to an ETS transcription factor. There have been seven reported chromosomal translocations, with the most recent reported over a decade ago. We now report a novel FET/ETS translocation involving FUS and ETV4 detected in a patient with Ewing sarcoma. Here, we characterized FUS/ETV4 by performing genomic localization and transcriptional regulatory studies on numerous FET/ETS fusions in a Ewing sarcoma cellular model. Through this comparative analysis, we demonstrate significant similarities across these fusions, and in doing so, validate FUS/ETV4 as a bona fide Ewing sarcoma translocation. This study presents the first genomic comparison of Ewing sarcoma‚Äďassociated translocations and reveals that the FET/ETS fusions share highly similar, but not identical, genomic localization and transcriptional regulation patterns. These data strengthen the notion that FET/ETS fusions are key drivers of, and thus pathognomonic for, Ewing sarcoma. Identification and initial characterization of the novel Ewing sarcoma fusion, FUS/ETV4, expands the family of Ewing fusions and extends the diagnostic possibilities for this aggressive tumor of adolescents and young adults.

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