Sankar Savita, Lessnick Stephen L
Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.
Cancer Genet. 2011 Jul;204(7):351-65. doi: 10.1016/j.cancergen.2011.07.008.
Ewing's sarcoma is a highly aggressive bone and soft tissue tumor of children and young adults. At the molecular genetic level Ewing's sarcoma is characterized by a balanced reciprocal translocation, t(11;22)(q24;q12), which encodes an oncogenic fusion protein and transcription factor EWS/FLI. This tumor-specific chimeric fusion retains the amino terminus of EWS, a member of the TET (TLS/EWS/TAF15) family of RNA-binding proteins, and the carboxy terminus of FLI, a member of the ETS family of transcription factors. In addition to EWS/FLI, variant translocation fusions belonging to the TET/ETS family have been identified in Ewing's sarcoma. These studies solidified the importance of TET/ETS fusions in the pathogenesis of Ewing's sarcoma and have since been used as diagnostic markers for the disease. EWS fusions with non-ETS transcription factor family members have been described in sarcomas that are clearly distinct from Ewing's sarcoma. However, in recent years there have been reports of rare fusions in "Ewing's-like tumors" that harbor the amino-terminus of EWS fused to the carboxy-terminal DNA or chromatin-interacting domains contributed by non-ETS proteins. This review aims to summarize the growing list of fusion oncogenes that characterize Ewing's sarcoma and Ewing's-like tumors and highlights important questions that need to be answered to further support the existing concept that Ewing's sarcoma is strictly a "TET/ETS" fusion-driven malignancy. Understanding the molecular mechanisms of action of the various different fusion oncogenes will provide better insights into the biology underlying this rare but important solid tumor.
尤因肉瘤是一种发生于儿童和青年的侵袭性很强的骨与软组织肿瘤。在分子遗传学水平上，尤因肉瘤的特征是一种平衡的相互易位，即t(11;22)(q24;q12)，它编码一种致癌融合蛋白和转录因子EWS/FLI。这种肿瘤特异性嵌合融合保留了RNA结合蛋白TET（TLS/EWS/TAF15）家族成员EWS的氨基末端，以及转录因子ETS家族成员FLI的羧基末端。除了EWS/FLI，在尤因肉瘤中还发现了属于TET/ETS家族的变异易位融合。这些研究证实了TET/ETS融合在尤因肉瘤发病机制中的重要性，此后一直被用作该疾病的诊断标志物。在与尤因肉瘤明显不同的肉瘤中，已描述了EWS与非ETS转录因子家族成员的融合。然而，近年来有报道称，在“尤因样肿瘤”中存在罕见融合，其具有EWS的氨基末端与非ETS蛋白贡献的羧基末端DNA或染色质相互作用结构域融合。本综述旨在总结越来越多的表征尤因肉瘤和尤因样肿瘤的融合致癌基因，并强调需要回答的重要问题，以进一步支持现有的概念，即尤因肉瘤严格来说是一种由“TET/ETS”融合驱动的恶性肿瘤。了解各种不同融合致癌基因的分子作用机制将为这种罕见但重要的实体瘤的生物学特性提供更好的见解。
