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　　基因融合一直被认为是肿瘤独有的特征。弗吉尼亚大学的一组研究人员从干细胞肌肉分化发生的融合基因事件入手，分析了横纹肌肉瘤细胞的起源，这是首次从融合基因的角度来研究肿瘤细胞的起源。

       基因融合一直被认为是肿瘤独有的特征。基因融合是指染色体上两个异位的基因嵌合在一起，这种现象一般是由于染色体发生易位、缺失或者倒置造成的，通常在癌症的发生发展扮演着重要的角色，并且可以作为诊断和治疗癌症的靶标。基因融合现象最早在慢性粒细胞白血病中 BCR-ABL基因融合。随着对基因融合的深入研究，科研人员发现，除血液系统肿瘤外，在实体瘤中也存在着基因融合现象，例如横纹肌肉瘤PAX3-FOXO1,前列腺癌中的TMPRSS2-ERG、小细胞肺癌中的EML4-ALK、结直肠癌中的VTI1A-TCF7L2，等基因融合。

       横纹肌肉瘤（Rhabdomyosarcoma，RMS）是罕见的一种恶性肿瘤，但在小儿实体瘤中发病率较高，其临床亚型有胚胎型横纹肌肉瘤（ERMS），腺泡型横纹肌肉瘤( ARMS)，在80－85%的ARMS中可检测到特异性染色体易位，两种易位分别形成相应的融合基因PAX3-FKHR(也称为PAX3-FOXO1)或PAX7-FOXO1。

        最新这项研究结合生物信息学和干细胞生物学，首次从融合基因的角度来研究肿瘤细胞的起源。在MSCs干细胞骨骼肌分化样品中发现有一个时间点样品和横纹肌肉瘤细胞RH30类似的融合基因组，这种瞬时的融合基因组发生事件提供了肿瘤细胞起源的新线索。

 原文摘要：

Fusion transcriptome profiling provides insights into alveolar rhabdomyosarcoma

Gene fusions and fusion products were thought to be unique features of neoplasia. However, more and more studies have identified fusion RNAs in normal physiology. Through RNA sequencing of 27 human noncancer tissues, a large number of fusion RNAs were found. By analyzing fusion transcriptome, we observed close clusterings between samples of same or similar tissues, supporting the feasibility of using fusion RNA profiling to reveal connections between biological samples. To put the concept into use, we selected alveolar rhabdomyosarcoma (ARMS), a myogenic pediatric cancer whose exact cell of origin is not clear. PAX3–FOXO1 (paired box gene 3 fused with forkhead box  O1) fusion RNA, which is considered a hallmark of ARMS, was recently found during normal muscle cell differentiation. We performed and analyzed RNA sequencing from various time points during myogenesis and uncovered many chimeric fusion RNAs. Interestingly, we found that the fusion RNA profile of RH30, an ARMS cell line, is most similar to the myogenesis time point when PAX3–FOXO1 is expressed. In contrast, full transcriptome clustering analysis failed to uncover this connection. Strikingly, all of the 18 chimeric RNAs in RH30 cells could be detected at the same myogenic time point(s). In addition, the seven chimeric RNAs that follow the exact transient expression pattern as PAX3–FOXO1 are specific to rhabdomyosarcoma cells. Further testing with clinical samples also confirmed their specificity to rhabdomyosarcoma. These results provide further support for the link between at least some ARMSs and the PAX3–FOXO1-expressing myogenic cells and demonstrate that fusion RNA profiling can be used to investigate the etiology of fusion-gene-associated cancers.