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–associated 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. Implications: 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.

中文翻译：

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一种新型 FUS/ETV4 融合蛋白的鉴定以及与其他尤文肉瘤融合蛋白的比较分析

尤文肉瘤是一种儿科骨癌，由将 FET 家族成员之一与 ETS 转录因子融合的染色体易位定义。已经报道了七次染色体易位，最近一次报道是在十多年前。我们现在报告在尤文肉瘤患者中检测到的涉及 FUS 和 ETV4 的新型 FET/ETS 易位。在这里，我们通过对尤文肉瘤细胞模型中的众多 FET/ETS 融合进行基因组定位和转录调控研究来表征 FUS/ETV4。通过这种比较分析，我们证明了这些融合之间的显着相似性，并以此验证 FUS/ETV4 是真正的尤文肉瘤易位。本研究首次对尤文肉瘤相关易位进行基因组比较，并揭示 FET/ETS 融合具有高度相似但不相同的基因组定位和转录调控模式。这些数据强化了 FET/ETS 融合是尤文肉瘤的关键驱动因素并因此成为其特征的观点。启示：新型尤文肉瘤融合FUS/ETV4的鉴定和初步表征扩大了尤文融合家族，并扩展了这种青少年和年轻人侵袭性肿瘤的诊断可能性。