Undifferentiated small round cell sarcomas with rare EWS gene fusions -: Identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV Fusions
Undifferentiated small round cell sarcomas with rare EWS gene fusions -: Identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV Fusions
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DOI：
10.2353/jmoldx.2007.070053
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发表时间：
2007-09-01
影响因子：
4.1
通讯作者：
Ladanyi, Marc
中科院分区：
文献类型：
--
作者：
Wang, Lu;Bhargava, Rohit;Ladanyi, Marc
尤文家族肿瘤（EFT）是发生于儿童或青少年骨骼或皮肤外软组织的典型原始小圆蓝细胞肉瘤。EfTs显示EWS与ETS家族转录因子基因的融合，EWS-FLI 1（90 - 95%）或EWS-ERG（5 - 10%）。EWS与其他ETS家族基因（如ETV 1、E1 AF和FEV）融合的罕见病例已被确定，但其与经典EFT的临床病理学相似性仍不清楚。我们报告了4例新的EFT样肿瘤与罕见的EWS融合，其中2例与EWS-ETV 1，1例与EWS-FEV，第四例中，我们克隆了一种新的EWS-SP3融合，第一个已知的癌症基因融合涉及Sp锌指家族的基因。对这3例新病例的分析沿着9例既往报告的EWS与EM、E1 AF或FEV融合病例的数据，提示强烈偏好皮肤外原发部位。EWS与非ETS易位伴侣融合的EFT样病例也不常见，但涉及EWS的相同氨基末端部分，在我们的新型EWS-SP3融合中，EWS与SP3锌指DNA结合结构域连接。这些数据进一步支持，这些类型的EWS融合与主要在儿科人群中出现的不确定谱系的原始皮肤外小圆细胞肉瘤相关。
Ewing family tumors (EFTs) are prototypical primitive small round blue cell sarcomas arising in bone or extraskeletal soft tissues in children or adolescents. EfTs show fusions of EWS with a gene of the ETS family of transcription factors, either EWS-FLI1 (90 to 95%) or EWS-ERG (5 to 10%). Rare cases with fusions of EWS to other ETS family genes, such as ETV1, E1AF, and FEV, have been identified, but their clinicopathological similarity to classic EFTs remains unclear. We report four new cases of EFT-like tumors with rare EWS fusions, including two with EWS-ETV1, one with EWS-FEV, and a fourth case in which we cloned a novel EWS-SP3 fusion, the first known cancer gene fusion involving a gene of the Sp zinc finger family. Analysis of these three new cases along with data on nine previously reported cases with fusions of EWS to EM, E1AF, or FEV suggest a strong predilection for extraskeletal primary sites. EFT-like cases with fusions of EWS to non-ETS translocation partners are also uncommon but involve the same amino-terminal portion of EWS, which in our novel EWS-SP3 fusion is joined to the SP3 zinc-finger DNA-binding domain. As these data further support, these types of EWS fusions are associated with primitive extraskeletal small round cell sarcomas of uncertain lineage arising mainly in the pediatric population.