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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.
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Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.

机译：增生性小圆形细胞瘤的EWS-WT1基因融合中的基因组断点和嵌合转录本的表征。

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摘要

Desmoplastic small round cell tumor is a recently recognized distinctive tumor shown to be associated with a recurrent translocation, t(11;22)(p13;q12), and rearrangement of the genes for Ewing sarcoma (EWS) and Wilms tumor (WT1). A genomic DNA fragment containing the EWS-WT1 gene fusion has been isolated from a desmoplastic small round cell tumor, and the breakpoint has been characterized. The breakpoints involve the intron between EWS exons 7 and 8 and the intron between WT1 exons 7 and 8. Chimeric transcripts corresponding to the fusion gene were detected in four of six cases studied. Analysis of these transcripts show an in-frame fusion of RNA encoding the amino-terminal domain of EWS to both alternatively spliced forms of the last three zinc fingers of the DNA-binding domain of WT1. Desmoplastic small round cell tumor represents the third tumor type associated with translocation of EWS and the first tumor associated with consistent translocation of WT1. The chimeric products are predicted to modulate transcription at WT1 target sites and contribute to development of this unique tumor.
机译：增塑小圆形细胞肿瘤是一种最近公认的独特肿瘤，显示与复发易位t（11; 22）（p13; q12）和尤因肉瘤（EWS）和Wilms肿瘤（WT1）的基因重排有关。从一个增生的小圆形细胞肿瘤中分离出了包含EWS-WT1基因融合体的基因组DNA片段，并对其断点进行了表征。断裂点涉及EWS外显子7和8之间的内含子和WT1外显子7和8之间的内含子。在研究的6例病例中有4例检测到了与融合基因相对应的嵌合转录物。这些转录物的分析显示，框内融合了编码EWS氨基末端结构域的RNA与WT1 DNA结合结构域的最后三个锌指的两种交替剪接形式。增生性小圆形细胞肿瘤代表与EWS易位相关的第三种肿瘤类型，以及与WT1持续易位相关的第一种肿瘤。嵌合产物预计将调节WT1靶位点的转录，并有助于这种独特肿瘤的发展。

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