Alternative titles; symbols
Other entities represented in this entry:
HGNC Approved Gene Symbol: SSX2
Cytogenetic location: Xp11.22 Genomic coordinates (GRCh38) : X:52,696,896-52,707,227 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| Xp11.22 | ?Sarcoma, synovial | 300813 | 3 |
Human synovial sarcomas (300813) contain a recurrent and specific chromosomal translocation t(X;18)(p11.2;q11.2). By screening a synovial sarcoma cDNA library with a YAC spanning the X chromosome breakpoint, Clark et al. (1994) identified a hybrid transcript that contained 5-prime sequences (which they designated SYT; see SS18, 600192) mapping to chromosome 18, and 3-prime sequences (which they designated SSX) mapping to the X chromosome. An SYT probe detected genomic rearrangements in 10 of 13 synovial sarcomas. Sequencing of cDNA clones showed that the normal SYT gene encodes a protein rich in glutamine, proline, and glycine and that in synovial sarcoma, rearrangement of the SYT gene results in the formation of an SYT-SSX fusion protein.
Crew et al. (1995) demonstrated that the t(X;18)(p11.2;q11.2) found in human synovial sarcoma results in the fusion of the chromosome 18 SS18 gene (SYT) to either of 2 distinct genes, SSX1 (312820) or SSX2 at Xp11.2. The SSX1 and SSX2 genes encode closely related proteins (81% identity) of 188 amino acids that are rich in charged amino acids. The N-terminal portion of each SSX protein exhibits homology to the Kruppel-associated box (KRAB), a transcriptional repressor domain previously found only in Kruppel-type zinc finger proteins, e.g., zinc finger protein-117 (ZNF117; 194624) and ZNF83 (194558). PCR analysis demonstrated the presence of SYT-SSX1 or SYT-SSX2 fusion transcripts in 29 of 32 synovial sarcomas examined, indicating that the detection of these hybrid transcripts by PCR may represent a useful diagnostic method. Sequence analysis demonstrated further heterogeneity in the fusion transcripts with the formation of 2 distinct SYT-SSX1 fusion junctions and 2 distinct SYT-SSX2 fusion junctions. Both the SYT-SSX1 and the SYT-SSX2 hybrid transcripts encode fusion proteins in which the C-terminal 8 amino acids of the normal SYT protein have been replaced by 78 amino acids encoded by an SSX gene. The SSX1 and SSX2 protein sequences present in these 2 fusion products have 66 of 78 amino acids in common.
The SYT-SSX1 form of synovial sarcoma, compared to the SYT-SSX2 form, has a significantly unfavorable prognosis (Kawai et al., 1998; Ladanyi et al., 2002). This suggests that the SYT-SSX fusion genes may influence molecular mechanisms involved in tumor growth and progression and that SYT-SSX1 has a stronger influence on these mechanisms than SYT-SSX2.
Clark et al. (1994) identified the SSX2 gene at the chromosome Xp11.2 breakpoint of the synovial sarcoma-related translocation t(X;18)(p11.2;q11.2).
Clark, J., Rocques, P. J., Crew, A. J., Gill, S., Shipley, J., Chan, A. M.-L., Gusterson, B. A., Cooper, C. S. Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nature Genet. 7: 502-508, 1994. [PubMed: 7951320] [Full Text: https://doi.org/10.1038/ng0894-502]
Crew, A. J., Clark, J., Fisher, C., Gill, S., Grimer, R., Chand, A., Shipley, J., Gusterson, B. A., Cooper, C. S. Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J. 14: 2333-2340, 1995. [PubMed: 7539744] [Full Text: https://doi.org/10.1002/j.1460-2075.1995.tb07228.x]
Kawai, A., Woodruff, J., Healey, J. H., Brennan, M. F., Antonescu, C. R., Ladanyi, M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. New Eng. J. Med. 338: 153-160, 1998. [PubMed: 9428816] [Full Text: https://doi.org/10.1056/NEJM199801153380303]
Ladanyi, M., Antonescu, C. R., Leung, D. H., Woodruff, J. M., Kawai, A., Healey, J. H., Brennan, M. F., Bridge, J. A., Neff, J. R., Barr, F. G., Goldsmith, J. D., Brooks, J. S. J., Goldblum, J. R., Ali, S. Z., Shipley, J., Cooper, C. S., Fisher, C., Skytting, B., Larsson, O. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. Cancer Res. 62: 135-140, 2002. [PubMed: 11782370]