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

The synovial sarcoma translocation t(X;18)(p11.2; q11.2) results in the fus ion 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 sequenc ed the full-length cDNA of SYT/SSX1, SYT/SSX2 and SYT/SSX4 from synovial sa rcoma 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 a nd SYT/SSX2 open reading frame also differed from previously reported SYT/S SX sequences by an in-frame addition of 93bp exon located in the junction b etween 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 o f SYT transcripts. This was also observed in a synovial sarcoma tumor expre ssing 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.