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Gene Review

SSX1  -  synovial sarcoma, X breakpoint 1

Homo sapiens

Synonyms: CT5.1, Cancer/testis antigen 5.1, Protein SSX1, SSRC, Synovial sarcoma, X breakpoint 1
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Disease relevance of SSX1

  • Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma [1].
  • SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs [2].
  • To determine the reason for this discrepancy, we analyzed cDNA from HS-SY-3 cells, as well as the original sarcoma tissue by the rapid amplification of cDNA 3' end assay, and found that the chimaeric cDNA was 240 bp shorter than the previously established SYT/SSX1 cDNA due to truncation of the 3' side of SSX1 [3].
  • Furthermore, the established RT-PCR protocol was used to evaluate the feasibility of SYT-SSX1/2 fusion transcript detection for minimal residual disease analysis [4].
  • Prompted by the frequent detection of SSX1 in a previous comprehensive expression profile of the Hodgkin's lymphoma (HL) cell line L428, we analyzed SSX expression by nonnested reverse-transcription polymerase chain reaction (RT-PCR) in 4 HL cell lines (L428, L540, HD-MY-Z, and KM-H2) and 32 tumor samples of HL [5].

High impact information on SSX1

  • 2. The SSX1 and SSX2 genes encode closely related proteins (81% identity) of 188 amino acids that are rich in charged amino acids [1].
  • We demonstrate that the cytogenetically defined translocation t(X;18)(p11.2;q11.2) found in human synovial sarcoma results in the fusion of the chromosome 18 SYT gene to either of two distinct genes, SSX1 or SSX2, at Xp11 [1].
  • A subset of synovial sarcoma, predominantly cases with the SYT-SSX1 fusion, shows foci of morphologic epithelial differentiation in the form of nests of glandular epithelium [6].
  • The translocation results in fusion of the SYT gene on chromosome 18 to either the SSX1 or the SSX2 gene, two homologous genes within Xp11 [7].
  • IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1 [8].

Chemical compound and disease context of SSX1

  • In the three cases, a reverse transcription-polymerase chain reaction (RT-PCR) using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX1 fusion gene transcripts resulting from translocation t(X;18)(p11.2;q11.2), which is specific for synovial sarcoma [9].

Biological context of SSX1


Anatomical context of SSX1


Other interactions of SSX1

  • Long-range organization of reiterated sequences, including the SSX1 cDNA at the OATL1 cluster in Xp11.23 [18].
  • The aims of this study were to determine the expression and immunogenicity of these antigens in patients with epithelial ovarian cancer (EOC).EXPERIMENTAL DESIGN: SSX-1-, SSX-2-, and SSX-4-specific reverse transcription-PCR were done on a panel of EOC specimens [19].
  • The SYT-SSX1 type fusion was associated with high Ki-67 expression (P = .011) and high mitotic rate (P = .070) [20].
  • Both neoplasms contained the SYT-SSX1 type of the diagnostic translocation t(X;18) as detected by the reverse-transcription polymerase chain reaction analysis [21].

Analytical, diagnostic and therapeutic context of SSX1


  1. Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. Crew, A.J., Clark, J., Fisher, C., Gill, S., Grimer, R., Chand, A., Shipley, J., Gusterson, B.A., Cooper, C.S. EMBO J. (1995) [Pubmed]
  2. SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs. Taylor, B.J., Reiman, T., Pittman, J.A., Keats, J.J., de Bruijn, D.R., Mant, M.J., Belch, A.R., Pilarski, L.M. J. Immunother. (2005) [Pubmed]
  3. A new human synovial sarcoma cell line, HS-SY-3, with a truncated form of hybrid SYT/SSX1 gene. Sonobe, H., Takeuchi, T., Liag, S.B., Taguchi, T., Yuri, K., Shimizu, K., Iwata, J., Furihata, M., Ohtsuki, Y., Testa, J.R. Int. J. Cancer (1999) [Pubmed]
  4. Detection of SYT-SSX1/2 fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) is a valuable diagnostic tool in synovial sarcoma. Willeke, F., Mechtersheimer, G., Schwarzbach, M., Weitz, J., Zimmer, D., Lehnert, T., Herfarth, C., von Knebel Doeberitz, M., Ridder, R. Eur. J. Cancer (1998) [Pubmed]
  5. Expression of SSX genes in the neoplastic cells of Hodgkin's lymphoma. Colleoni, G.W., Capodieci, P., Tickoo, S., Cossman, J., Filippa, D.A., Ladanyi, M. Hum. Pathol. (2002) [Pubmed]
  6. SYT-SSX1 and SYT-SSX2 interfere with repression of E-cadherin by snail and slug: a potential mechanism for aberrant mesenchymal to epithelial transition in human synovial sarcoma. Saito, T., Nagai, M., Ladanyi, M. Cancer Res. (2006) [Pubmed]
  7. Interphase fluorescence in situ hybridization and reverse transcription polymerase chain reaction as a diagnostic aid for synovial sarcoma. Shipley, J., Crew, J., Birdsall, S., Gill, S., Clark, J., Fisher, C., Kelsey, A., Nojima, T., Sonobe, H., Cooper, C., Gusterson, B. Am. J. Pathol. (1996) [Pubmed]
  8. IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1. Sun, Y., Gao, D., Liu, Y., Huang, J., Lessnick, S., Tanaka, S. Oncogene (2006) [Pubmed]
  9. Synovial sarcomas of three children in the first decade: clinicopathological and molecular findings. Okamoto, S., Ishida, T., Ohnishi, H., MacHinami, R., Hashimoto, H. Pathol. Int. (2000) [Pubmed]
  10. A novel fusion gene, SS18L1/SSX1, in synovial sarcoma. Storlazzi, C.T., Mertens, F., Mandahl, N., Gisselsson, D., Isaksson, M., Gustafson, P., Domanski, H.A., Panagopoulos, I. Genes Chromosomes Cancer (2003) [Pubmed]
  11. Molecular mechanisms underlying human synovial sarcoma development. dos Santos, N.R., de Bruijn, D.R., van Kessel, A.G. Genes Chromosomes Cancer (2001) [Pubmed]
  12. SSX: a multigene family with several members transcribed in normal testis and human cancer. Gure, A.O., Türeci, O., Sahin, U., Tsang, S., Scanlan, M.J., Jäger, E., Knuth, A., Pfreundschuh, M., Old, L.J., Chen, Y.T. Int. J. Cancer (1997) [Pubmed]
  13. A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas. Lim, F.L., Soulez, M., Koczan, D., Thiesen, H.J., Knight, J.C. Oncogene (1998) [Pubmed]
  14. The SYT-SSX1 fusion type of synovial sarcoma is associated with increased expression of cyclin A and D1. A link between t(X;18)(p11.2; q11.2) and the cell cycle machinery. Xie, Y., Skytting, B., Nilsson, G., Grimer, R.J., Mangham, C.D., Fisher, C., Shipley, J., Bjerkehagen, B., Myklebost, O., Larsson, O. Oncogene (2002) [Pubmed]
  15. The SSX gene family: characterization of 9 complete genes. Güre, A.O., Wei, I.J., Old, L.J., Chen, Y.T. Int. J. Cancer (2002) [Pubmed]
  16. A novel Krüppel-associated box containing the SSX gene (SSX3) on the human X chromosome is not implicated in t(X;18)-positive synovial sarcomas. de Leeuw, B., Balemans, M., Geurts van Kessel, A. Cytogenet. Cell Genet. (1996) [Pubmed]
  17. Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma. van de Rijn, M., Barr, F.G., Collins, M.H., Xiong, Q.B., Fisher, C. Am. J. Clin. Pathol. (1999) [Pubmed]
  18. Long-range organization of reiterated sequences, including the SSX1 cDNA at the OATL1 cluster in Xp11.23. Chand, A., Clark, J., Cooper, C.S., Craig, I.W. Genomics (1995) [Pubmed]
  19. Expression of synovial sarcoma X (SSX) antigens in epithelial ovarian cancer and identification of SSX-4 epitopes recognized by CD4+ T cells. Valmori, D., Qian, F., Ayyoub, M., Renner, C., Merlo, A., Gnjatic, S., Gjnatic, S., Stockert, E., Driscoll, D., Lele, S., Old, L.J., Odunsi, K. Clin. Cancer Res. (2006) [Pubmed]
  20. Association of SYT-SSX fusion types with proliferative activity and prognosis in synovial sarcoma. Inagaki, H., Nagasaka, T., Otsuka, T., Sugiura, E., Nakashima, N., Eimoto, T. Mod. Pathol. (2000) [Pubmed]
  21. Late solitary bone metastasis of a primary pulmonary synovial sarcoma with SYT-SSX1 translocation type: case report with a long follow-up. Bode-Lesniewska, B., Hodler, J., von Hochstetter, A., Guillou, L., Exner, U., Caduff, R. Virchows Arch. (2005) [Pubmed]
  22. Dual colour fluorescence in situ hybridization to paraffin-embedded samples to deduce the presence of the der(X)t(X;18)(p11.2;q11.2) and involvement of either the SSX1 or SSX2 gene: a diagnostic and prognostic aid for synovial sarcoma. Lu, Y.J., Birdsall, S., Summersgill, B., Smedley, D., Osin, P., Fisher, C., Shipley, J. J. Pathol. (1999) [Pubmed]
  23. Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/neu in synovial sarcoma. Thomas, D.G., Giordano, T.J., Sanders, D., Biermann, S., Sondak, V.K., Trent, J.C., Yu, D., Pollock, R.E., Baker, L. Cancer (2005) [Pubmed]
  24. Molecular diagnosis of synovial sarcoma: RT-PCR detection of SYT-SSX1/2 fusion transcripts in paraffin-embedded tissue. Tvrdík, D., Povýsil, C., Svatosová, J., Dundr, P. Med. Sci. Monit. (2005) [Pubmed]
  25. A poorly differentiated synovial sarcoma (SYT/SSX1) expresses neuroectodermal markers: a xenografts and in vitro culture study. Rosa, N., Samuel, N., Lopez-Guerrero, n.u.l.l., Antonio, J., Carmen, C., Antonio, P., Antonio, L.B. Diagn. Mol. Pathol. (2004) [Pubmed]
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