Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Genes Chromosomes Cancer. 2020 May;59(5):286-294. doi: 10.1002/gcc.22828. Epub 2019 Dec 3.
The molecular hallmark of Ewing sarcoma (ES) is a fusion involving the EWSR1 gene and a member of the ETS family of transcription factors. EWSR1-FLI1 is the most common variant, occurring in 90% of cases, followed by EWSR1-ERG. In a small subset, the FUS gene can substitute for EWSR1 in these fusions. Only rare case reports have been described to date of ES with FEV gene rearrangements. In this study, we investigate the clinicopathologic and molecular features of 10 ES patients with FEV-rearrangements, either fused to EWSR1 (n = 4) or to FUS (n = 6). The median age at diagnosis was 38 years (range, 5-61 years); occurring in six males and four females. All tumors were located at extraskeletal sites, occurring more often in the axial soft tissues. Tumors had a similar morphologic appearance and immunophenotype as ES with more common EWSR1-ETS fusions. Of six patients with follow-up data, five patients (83%) developed metastasis and two patients (33%) died of their diseases. The diagnosis was confirmed either by fluorescence in situ hybridization and/or targeted RNA sequencing. In the five cases tested by targeted sequencing, the fusion transcripts were composed of EWSR1 or FUS fused to either exon 1 or 2 of FEV, retaining the FEV ETS DNA binding domain. This is the largest study to date investigating the ES subset with EWSR1/FUS-FEV fusions showing a predilection for extraskeletal sites and aggressive behavior.
尤因肉瘤（Ewing sarcoma，ES）的分子特征是涉及 EWSR1 基因和 ETS 家族转录因子成员的融合。EWSR1-FLI1 是最常见的变异型，发生在 90%的病例中，其次是 EWSR1-ERG。在一小部分病例中，FUS 基因可以替代这些融合中的 EWSR1。迄今为止，只有少数关于 ES 伴 FEV 基因重排的病例报告。在这项研究中，我们研究了 10 例伴有 FEV 重排的 ES 患者的临床病理和分子特征，这些患者要么与 EWSR1 融合（n = 4），要么与 FUS 融合（n = 6）。诊断时的中位年龄为 38 岁（范围，5-61 岁）；男性 6 例，女性 4 例。所有肿瘤均位于骨外部位，更多发生在轴性软组织中。肿瘤具有与具有更常见的 EWSR1-ETS 融合的 ES 相似的形态学表现和免疫表型。在有随访数据的 6 例患者中，5 例（83%）发生转移，2 例（33%）死于疾病。诊断结果通过荧光原位杂交和/或靶向 RNA 测序得到确认。在通过靶向测序测试的 5 例病例中，融合转录本由 EWSR1 或 FUS 与 FEV 的外显子 1 或 2 融合而成，保留了 FEV ETS DNA 结合域。这是迄今为止研究 EWSR1/FUS-FEV 融合的 ES 亚组的最大研究，该亚组表现出对骨外部位和侵袭性行为的偏好。
