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Gene Review

SSX2  -  synovial sarcoma, X breakpoint 2

Homo sapiens

Synonyms: CT5.2, CT5.2A, CT5.2a, HD21, HOM-MEL-40, ...
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Disease relevance of SSX2

  • Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma [1].
  • Three of the 13 antigens were cancer/testis antigens (MAGEA3, SSX2, and NY-ESO-1), which are expressed exclusively in normal gametogenic tissues and aberrantly expressed in a broad range of cancer types [2].
  • To define additional CT antigens, we have immuno-screened a testicular cDNA expression library with an allogeneic serum from a melanoma patient, and both SSX2 and SSX3 were isolated [3].
  • Thirty-four of 101 primary and metastatic melanoma cases and 2 of 24 common nevocellular and atypical nevus cases showed SSX nuclear staining [4].
  • Fifteen other sarcomas and related tumors were negative for SYT-SSX fusion transcripts [5].

High impact information on SSX2

  • SYT sequences constitute the N-terminal segment of a fusion oncogene product, SYT-SSX, routinely detected in synovial sarcoma, an aggressive human tumor [6].
  • The translocation fuses the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1 or SSX2 [7].
  • SYT-SSX fusion transcripts are a defining diagnostic marker of synovial sarcomas and may also yield important independent prognostic information [7].
  • SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma [7].
  • There were no significant correlations between the type of SYT-SSX transcript and age, sex, tumor location and size, whether there were metastases at diagnosis, or whether patients underwent chemotherapy [7].

Chemical compound and disease context of SSX2


Biological context of SSX2

  • As a result of this translocation the SYT gene on chromosome 18 fuses to either the SSX1 or the SSX2 gene on the X chromosome [10].
  • Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8) [11].
  • Genomic cloning of a prototype SSX gene (SSX2) showed that its coding region is encoded by 6 exons, and the shortened form of SSX4 cDNA represents an alternatively spliced product lacking the 5th exon [3].
  • Treatment of an SSX-negative cell line with 5-aza-2'-deoxycytidine, a demethylating agent, led to SSX RNA and protein expression, indicating a role for methylation in transcription regulation [4].
  • We now report the analysis of the expression of all 5 SSX genes in 325 specimens of human neoplasms from various histological origins, using reverse transcription polymerase chain reaction (RT-PCR) [12].

Anatomical context of SSX2


Associations of SSX2 with chemical compounds

  • The SYT-SSX2 fusion transcripts were detected by a reverse transcription-polymerase chain reaction (RT-PCR) using RNA extracted from formalin-fixed, paraffin-embedded tissue [15].

Physical interactions of SSX2


Co-localisations of SSX2

  • Likewise, the SSX2IP protein was found to be colocalizing with SSX2 in the nucleus [16].

Regulatory relationships of SSX2

  • Seventy-two percent (13/18) of stage 4 NB expressed SSX-2 and 67% (12/18) expressed SSX-4 [17].

Other interactions of SSX2


Analytical, diagnostic and therapeutic context of SSX2


  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. Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets. Scanlan, M.J., Welt, S., Gordon, C.M., Chen, Y.T., Gure, A.O., Stockert, E., Jungbluth, A.A., Ritter, G., Jäger, D., Jäger, E., Knuth, A., Old, L.J. Cancer Res. (2002) [Pubmed]
  3. 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]
  4. Heterogeneous expression of the SSX cancer/testis antigens in human melanoma lesions and cell lines. dos Santos, N.R., Torensma, R., de Vries, T.J., Schreurs, M.W., de Bruijn, D.R., Kater-Baats, E., Ruiter, D.J., Adema, G.J., van Muijen, G.N., van Kessel, A.G. Cancer Res. (2000) [Pubmed]
  5. Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma. Lasota, J., Jasinski, M., Debiec-Rychter, M., Szadowska, A., Limon, J., Miettinen, M. Mod. Pathol. (1998) [Pubmed]
  6. p300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion. Eid, J.E., Kung, A.L., Scully, R., Livingston, D.M. Cell (2000) [Pubmed]
  7. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. Kawai, A., Woodruff, J., Healey, J.H., Brennan, M.F., Antonescu, C.R., Ladanyi, M. N. Engl. J. Med. (1998) [Pubmed]
  8. Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues. Tsuji, S., Hisaoka, M., Morimitsu, Y., Hashimoto, H., Shimajiri, S., Komiya, S., Ushijima, M., Nakamura, T. Am. J. Pathol. (1998) [Pubmed]
  9. Detection of SYT-SSX fusion transcripts in both epithelial and spindle cell areas of biphasic synovial sarcoma using laser capture microdissection. Kasai, T., Shimajiri, S., Hashimoto, H. MP, Mol. Pathol. (2000) [Pubmed]
  10. Nuclear localization of SYT, SSX and the synovial sarcoma-associated SYT-SSX fusion proteins. dos Santos, N.R., de Bruijn, D.R., Balemans, M., Janssen, B., Gärtner, F., Lopes, J.M., de Leeuw, B., Geurts van Kessel, A. Hum. Mol. Genet. (1997) [Pubmed]
  11. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients. 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., Goldblum, J.R., Ali, S.Z., Shipley, J., Cooper, C.S., Fisher, C., Skytting, B., Larsson, O. Cancer Res. (2002) [Pubmed]
  12. Expression of SSX genes in human tumors. Türeci, O., Chen, Y.T., Sahin, U., Güre, A.O., Zwick, C., Villena, C., Tsang, S., Seitz, G., Old, L.J., Pfreundschuh, M. Int. J. Cancer (1998) [Pubmed]
  13. SYT-SSX fusion genes in synovial sarcoma of the thorax. Yano, M., Toyooka, S., Tsukuda, K., Dote, H., Morimoto, Y., Ohata, N., Ichimura, K., Aoe, M., Date, H., Shimizu, N. Lung Cancer (2004) [Pubmed]
  14. 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]
  15. Primary synovial sarcoma of the kidney: Report of a case confirmed by molecular detection of the SYT-SSX2 fusion transcripts. Koyama, S., Morimitsu, Y., Morokuma, F., Hashimoto, H. Pathol. Int. (2001) [Pubmed]
  16. The cancer-related protein SSX2 interacts with the human homologue of a Ras-like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP. de Bruijn, D.R., dos Santos, N.R., Kater-Baats, E., Thijssen, J., van den Berk, L., Stap, J., Balemans, M., Schepens, M., Merkx, G., van Kessel, A.G. Genes Chromosomes Cancer (2002) [Pubmed]
  17. Expression of SSX-2 and SSX-4 genes in neuroblastoma. Chi, S.N., Cheung, N.K., Cheung, I.Y. Int. J. Biol. Markers (2002) [Pubmed]
  18. 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]
  19. Molecular diagnosis of synovial sarcoma and characterization of a variant SYT-SSX2 fusion transcript. Fligman, I., Lonardo, F., Jhanwar, S.C., Gerald, W.L., Woodruff, J., Ladanyi, M. Am. J. Pathol. (1995) [Pubmed]
  20. 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]
  21. Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Atanackovic, D., Arfsten, J., Cao, Y., Gnjatic, S., Schnieders, F., Bartels, K., Schilling, G., Faltz, C., Wolschke, C., Dierlamm, J., Ritter, G., Eiermann, T., Hossfeld, D.K., Zander, A.R., Jungbluth, A.A., Old, L.J., Bokemeyer, C., Kröger, N. Blood (2007) [Pubmed]
  22. A novel case of synovial sarcoma of the kidney: impact of SS18/SSX analysis of renal hemangiopericytoma-like tumors. Törnkvist, M., Wejde, J., Ahlén, J., Brodin, B., Larsson, O. Diagn. Mol. Pathol. (2004) [Pubmed]
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