GENE FUSION WITH AN ETS DNA-BINDING DOMAIN CAUSED BY CHROMOSOME-TRANSLOCATION IN HUMAN TUMORS
GENE FUSION WITH AN ETS DNA-BINDING DOMAIN CAUSED BY CHROMOSOME-TRANSLOCATION IN HUMAN TUMORS
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DOI：
10.1038/359162a0
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发表时间：
1992-09-10
期刊：
影响因子：
64.8
通讯作者：
THOMAS, G
中科院分区：
文献类型：
--
作者：
DELATTRE, O;ZUCMAN, J;THOMAS, G
尤文氏肉瘤和原始神经外胚层肿瘤的相关亚型具有复发性和特异性t(11; 22) （q24; q12）染色体易位1-8，其断点最近已被克隆9。在染色体22和11的断点所在的基因组区域EWSR1和EWSR2附近存在系统发育上保守的限制性内切片段，这使得从这些区域鉴定转录序列成为可能，并表明该易位可能产生杂交转录物9。在这里，我们使用这些片段筛选人类互补DNA文库，以表明易位通过将编码假定rna结合域的序列替换为小鼠fl -1的人类同源物的DNA结合域的序列，从而改变了22号染色体上表达基因的开放阅读框。
EWING'S sarcoma and related subtypes of primitive neuroectodermal tumours share a recurrent and specific t(11; 22) (q24; q12) chromosome translocation1-8, the breakpoints of which have recently been cloned9. Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation9. Here we use these fragments to screen human complementary DNA libraries to show that the translocation alters the open reading frame of an expressed gene on chromosome 22 gene by substituting a sequence encoding a putative RNA-binding domain for that of the DNA-binding domain of the human homologue of murine Fli-1.