Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation
Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation
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DOI：
10.1038/sj.onc.1202364
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发表时间：
1999-01-21
期刊：
影响因子：
8
通讯作者：
Toguchida, J
中科院分区：
文献类型：
--
作者：
Kanoe, H;Nakayama, T;Toguchida, J
通过相互易位t(12;16)（q32;q16）融合TLS/FUS和CHOP基因是黏液样和圆细胞脂肪肉瘤中常见的遗传事件，通过Southern blot、RT-PCR和基因组远程PCR三种方法对9例黏液样和3例圆细胞脂肪肉瘤进行了该遗传事件的表征。除1例肿瘤外，其余肿瘤均出现了TLS/FUS与CHOP基因融合的遗传改变，发现了2种新型的融合转录本，其中1种缺失CHOP基因2外显子序列，另1种缺失TLS基因5外显子3′半，后者是由基因组融合产生的一个隐剪接位点引起的，详细分析了基因组融合点周围的一些序列特征。对已知序列基序的断点序列进行同源性分析，可能涉及两种情况下在TLS/ FUS和CHOP断点上发现Translin结合序列的易位过程。易位总是与其他遗传改变有关，如缺失、重复或插入。短的直接重复几乎总是在删除或复制片段的两端发现，其中一些片段显然是通过连接重排两侧的序列而产生的。最后，在所有分析的病例中，都在断点处发现了拓扑异构酶II的切割位点，这表明该酶在断点处产生交错末端的作用。这些数据表明，在脂肪肉瘤的染色体翻译过程中，序列特征可能在吸收Translin和拓扑异构酶II等多种因子方面发挥重要作用。
Fusion of TLS/FUS and CHOP gene by reciprocal translocation t(12;16)(q32;q16) is a common genetic event found in myxoid and round-cell liposarcomas, Characterization of this genetic event was performed by three methods, Southern blot, RT-PCR, and genomic long-distance PCR in nine myxoid and three round-cell liposarcomas. All but one tumors showed genetic alternations indicating the fusion of TLS/FUS and CHOP gene, Two novel types of fusion transcripts were found, of which one lacked exon 2 sequence of CHOP gene, and the other lacked 3' half of exon 5 of TLS gene, The latter case was caused by a cryptic splicing site which,vas created by the genomic fusion, Detailed analyses genomic fusion points revealed several sequence characteristics surrounding the fusion points, Homology analyses of breakpoint sequences with known sequence motifs possibly involve in the process of translocation uncovered Translin binding sequences at both of TLS/ FUS and CHOP breakpoints in two cases. Translocations were always associated with other genetic alterations, such as deletions, duplications, or insertions. Short direct repeats were almost always found at both ends of deleted or duplicated fragments some of which had apparently been created by joining of sequences that flank the rearrangement. Finally, consensus topoisomerase II cleavage sites were found at breakpoints in all cases analysed, suggesting a role of this enzyme in creating staggered ends at the breakpoint, These data suggested that sequence characteristics may play an important role to recruit several factors such as Translin and topoisomerase II in the process of chromosomal translation in liposarcomas.