Cloning and characterization of spliced fusion transcript variants of synovial sarcoma: SYT/SSX4, SYT/SSX4v, and SYT/SSX2v. Possible regulatory role of the fusion gene product in wild type SYT expression
Cloning and characterization of spliced fusion transcript variants of synovial sarcoma: SYT/SSX4, SYT/SSX4v, and SYT/SSX2v. Possible regulatory role of the fusion gene product in wild type SYT expression
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DOI：
10.1016/s0378-1119(01)00412-7
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发表时间：
2001-05-02
期刊：
影响因子：
3.5
通讯作者：
Larsson, O
中科院分区：
文献类型：
--
作者：
Brodin, B;Haslam, K;Larsson, O
滑膜肉瘤易位t（X;18）（p11.2; q11.2）导致18号染色体上的SYT基因与X号染色体上SSX 1或SSX 2基因的外显子5融合。我们最近报道，SSX 4基因也参与了这样的易位。本研究从滑膜肉瘤组织中克隆了SYT/SSX 1、SYT/SSX 2和SYT/SSX 4的全长cDNA并进行了序列测定。我们分离了一种新的融合转录型变体，涉及SYT与SSX 4基因的外显子6的融合（SYT/SSX 4v）。SYT/SSX 4和SYT/SSX 2的开放阅读框也不同于先前报道的SYT/SSX序列，因为在SYT的外显子7和8之间的连接处增加了93 bp的外显子。该外显子与所报道的鼠SYT外显子相同，但以前未在人转录本中发现。两个SYT的转录本，有和没有93 bp的外显子，共表达在小鼠NIH 3 T3细胞，人恶性肿瘤细胞和人睾丸组织，但没有在人正常成纤维细胞。SYT/SSX 4表达载体稳定转染人和鼠细胞系与SYT转录物的下调相关。这也在表达SYT/SSX 4的滑膜肉瘤肿瘤中观察到。这表明SYT/SSX融合基因可以调节SYT从正常等位基因的表达，并因此改变SYT的正常功能。(C)2001爱思唯尔科技有限公司。保留所有权利。
The synovial sarcoma translocation t(X;18)(p11.2; q11.2) results in the fusion of the SYT gene on chromosome 18 to exon 5 of either SSX1 or SSX2 genes on chromosome X. We recently reported that the SSX4 gene is also involved in such a translocation. In the present investigation we cloned and sequenced the full-length cDNA of SYT/SSX1, SYT/SSX2 and SYT/SSX4 from synovial sarcoma tissues. We isolated a novel fusion transcript type Variant involving the fusion of SYT with exon 6 of the SSX4 gene (SYT/SSX4v). The SYT/SSX4 and SYT/SSX2 open reading frame also differed from previously reported SYT/SSX sequences by an in-frame addition of 93bp exon located in the junction between exon 7 and 8 of the SYT. This exon is identical to that reported for the murine SYT but has not been previously found in the human transcript. Two SYT transcripts, with and without the 93 bp exon, were co-expressed in mouse NIH3T3 cells, human malignant cells and human testis tissue, but not in human normal fibroblasts. Stable transfection of an SYT/SSX4 expression vector into human and murine cell lines correlated with a down-regulation of SYT transcripts. This was also observed in a synovial sarcoma tumor expressing SYT/SSX4. This suggests that the SYT/SSX fusion gene may regulate SYT expression from the normal allele and as such alter the normal function of SYT. (C) 2001 Elsevier Science B.V. All rights reserved.