Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma

Abstract

Human synovial sarcomas contain a recurrent and specific chromosomal translocation t(X;18)(p11.2;q11.2). By screening a synovial sarcoma cDNA library with a yeast artificial chromosome spanning the X chromosome breakpoint, we have identified a hybrid transcript that contains 5' sequences (designated SYT) mapping to chromosome 18 and 3' sequences (designated SSX) mapping to chromosome X. An SYT probe detected genomic rearrangements in 10/13 synovial sarcomas. Sequencing of cDNA clones shows that the normal SYT gene encodes a protein rich in glutamine, proline and glycine, and indicates that in synovial sarcoma rearrangement of the SYT gene results in the formation of an SYT-SSX fusion protein. Both SYT and SSX failed to exhibit significant homology to known gene sequences.

Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma

“…Preparation of genomic DNA and cytoplasmic RNA were carried out as described (Clark et al, 1994). Restriction Detection of PSF-TFE3 and NonO-TFE3 hybrid transcripts by RT ± PCR (upper two panels).…”

“…RNAs used for these experiments were from the UOK109 and UOK145 papillary renal cell carcinoma cell lines and the following human tumor samples; the HA2243 synovial sarcoma cell line; the SK23 melanoma cell line; the RD rhabdomyosarcoma cell lines; and the HTB86 Ewings sarcoma cell line endonuclease digestions and Southern blot analysis were carried out as described previously. (Clark et al, 1994).…”

A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas

“…This novel domain is conserved between SSX family members, and, unlike the KRAB-related domain, is retained on fusion with SYT. This has important implications in understanding the mechanism by which the SYT-SSX fusion protein could contribute to neoplasia.Keywords: sarcoma; SSX; KRAB; transcription Chromosome translocation t(X;18)(p11.2;q11.2) (Clark et al, 1994;Crew et al, 1995) is a diagnostic feature of human synovial sarcomas, in some cases representing the sole cytogenetic abnormality (Sandberg and Bridge, 1994). All the available evidence indicates that this translocation is a key event in tumorigenesis.…”

“…Keywords: sarcoma; SSX; KRAB; transcription Chromosome translocation t(X;18)(p11.2;q11.2) (Clark et al, 1994;Crew et al, 1995) is a diagnostic feature of human synovial sarcomas, in some cases representing the sole cytogenetic abnormality (Sandberg and Bridge, 1994). All the available evidence indicates that this translocation is a key event in tumorigenesis.…”

“…In all the SYT-SSX1 and SYT-SSX2 fusion transcripts analysed, this KRAB domain is deleted and replaced with SYT sequence (see Figure 1). Transcripts of the reciprocal SSX-SYT fusion gene, which would be predicted to juxtapose the SSX-KRAB domain with the C-terminal eight amino acids of SYT (see Figure 1), are not detectable (Clark et al, 1994). Brett et al, (1997) have reported that full-length SSX1 exerts transcriptional repression and attribute this to the KRAB domain.…”