Abstract
Synovial sarcoma (SS) is cytogenetically characterized by the translocation t(X;18)(p11.2-q11.2) generating a fusion between the SYT gene on chromosome 18 and one member of the SSX family gene (SSX1; SSX2; SSX4) on chromosome X. Here, we report for the first time that 2 forms of SYT mRNA are present in both normal tissues and SSs. By amplifying the full-length SYT cDNA of two SSs, we detected 2 bands, here designated N-SYT and I-SYT. The latter, previously undescribed, contains an in-frame insertion of 93 bp. Its sequencing revealed a 100% homology with the mouse SYT gene. These two SYT forms were present, although in different amounts, in all human normal tissues examined, including kidney, stomach, lung, colon, liver and synovia. Coexistence of N-SYT and I-SYT (both fused with SSX) was detected in a series of 59 SSs (35 monophasic and 24 biphasic) and in a SS cell line. A preliminary analysis of the differential expression levels of N-SYT and I-SYT in SSs revealed that the latter was consistently overexpressed, suggesting a role in SS pathogenesis. © 2001 Cancer Research Campaign http://www.bjcancer.com
Keywords: synovial sarcoma, fusion transcript, RT-PCR analysis, alternative splicing event
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- Antonescu C. R., Kawai A., Leung D. H., Lonardo F., Woodruff J. M., Healey J. H., Ladanyi M. Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma. Diagn Mol Pathol. 2000 Mar;9(1):1–8. doi: 10.1097/00019606-200003000-00001. [DOI] [PubMed] [Google Scholar]
- Brett D., Whitehouse S., Antonson P., Shipley J., Cooper C., Goodwin G. The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies. Hum Mol Genet. 1997 Sep;6(9):1559–1564. doi: 10.1093/hmg/6.9.1559. [DOI] [PubMed] [Google Scholar]
- 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. 1995 May 15;14(10):2333–2340. doi: 10.1002/j.1460-2075.1995.tb07228.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fetsch J. F., Meis J. M. Synovial sarcoma of the abdominal wall. Cancer. 1993 Jul 15;72(2):469–477. doi: 10.1002/1097-0142(19930715)72:2<469::aid-cncr2820720224>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
- Fisher C. Synovial sarcoma: ultrastructural and immunohistochemical features of epithelial differentiation in monophasic and biphasic tumors. Hum Pathol. 1986 Oct;17(10):996–1008. doi: 10.1016/s0046-8177(86)80083-1. [DOI] [PubMed] [Google Scholar]
- Fritsch M., Epstein J. I., Perlman E. J., Watts J. C., Argani P. Molecularly confirmed primary prostatic synovial sarcoma. Hum Pathol. 2000 Feb;31(2):246–250. doi: 10.1016/s0046-8177(00)80228-2. [DOI] [PubMed] [Google Scholar]
- Gure A. O., Türeci O., Sahin U., Tsang S., Scanlan M. J., Jäger E., Knuth A., Pfreundschuh M., Old L. J., Chen Y. T. SSX: a multigene family with several members transcribed in normal testis and human cancer. Int J Cancer. 1997 Sep 17;72(6):965–971. doi: 10.1002/(sici)1097-0215(19970917)72:6<965::aid-ijc8>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- Hisaoka M., Hashimoto H., Iwamasa T., Ishikawa K., Aoki T. Primary synovial sarcoma of the lung: report of two cases confirmed by molecular detection of SYT-SSX fusion gene transcripts. Histopathology. 1999 Mar;34(3):205–210. doi: 10.1046/j.1365-2559.1999.00630.x. [DOI] [PubMed] [Google Scholar]
- Karn C. M., Socinski M. A., Fletcher J. A., Corson J. M., Craighead J. E. Cardiac synovial sarcoma with translocation (X;18) associated with asbestos exposure. Cancer. 1994 Jan 1;73(1):74–78. doi: 10.1002/1097-0142(19940101)73:1<74::aid-cncr2820730114>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
- Kashima T., Matsushita H., Kuroda M., Takeuchi H., Udagawa H., Ishida T., Hara M., Machinami R. Biphasic synovial sarcoma of the peritoneal cavity with t(X;18) demonstrated by reverse transcriptase polymerase chain reaction. Pathol Int. 1997 Sep;47(9):637–641. doi: 10.1111/j.1440-1827.1997.tb04555.x. [DOI] [PubMed] [Google Scholar]
- 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. N Engl J Med. 1998 Jan 15;338(3):153–160. doi: 10.1056/NEJM199801153380303. [DOI] [PubMed] [Google Scholar]
- Lim F. L., Soulez M., Koczan D., Thiesen H. J., Knight J. C. A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas. Oncogene. 1998 Oct 15;17(15):2013–2018. doi: 10.1038/sj.onc.1202122. [DOI] [PubMed] [Google Scholar]
- Mancuso T., Mezzelani A., Riva C., Fabbri A., Dal Bo L., Sampietro G., Perego P., Casali P., Zunino F., Sozzi G. Analysis of SYT-SSX fusion transcripts and bcl-2 expression and phosphorylation status in synovial sarcoma. Lab Invest. 2000 Jun;80(6):805–813. doi: 10.1038/labinvest.3780085. [DOI] [PubMed] [Google Scholar]
- Miloro M., Quinn P. D., Stewart J. C. Monophasic spindle cell synovial sarcoma of the head and neck: report of two cases an review of the literature. J Oral Maxillofac Surg. 1994 Mar;52(3):309–313. doi: 10.1016/0278-2391(94)90308-5. [DOI] [PubMed] [Google Scholar]
- Nicholson A. G., Goldstraw P., Fisher C. Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathological and immunohistochemical review of three cases. Histopathology. 1998 Dec;33(6):508–513. doi: 10.1046/j.1365-2559.1998.00565.x. [DOI] [PubMed] [Google Scholar]
- Nielsen G. P., Shaw P. A., Rosenberg A. E., Dickersin G. R., Young R. H., Scully R. E. Synovial sarcoma of the vulva: a report of two cases. Mod Pathol. 1996 Oct;9(10):970–974. [PubMed] [Google Scholar]
- Renwick P. J., Reeves B. R., Dal Cin P., Fletcher C. D., Kempski H., Sciot R., Kazmierczak B., Jani K., Sonobe H., Knight J. C. Two categories of synovial sarcoma defined by divergent chromosome translocation breakpoints in Xp11.2, with implications for the histologic sub-classification of synovial sarcoma. Cytogenet Cell Genet. 1995;70(1-2):58–63. doi: 10.1159/000133992. [DOI] [PubMed] [Google Scholar]
- Skytting B., Nilsson G., Brodin B., Xie Y., Lundeberg J., Uhlén M., Larsson O. A novel fusion gene, SYT-SSX4, in synovial sarcoma. J Natl Cancer Inst. 1999 Jun 2;91(11):974–975. doi: 10.1093/jnci/91.11.974. [DOI] [PubMed] [Google Scholar]
- Strubin M., Newell J. W., Matthias P. OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins. Cell. 1995 Feb 10;80(3):497–506. doi: 10.1016/0092-8674(95)90500-6. [DOI] [PubMed] [Google Scholar]
- Tamkun J. W., Deuring R., Scott M. P., Kissinger M., Pattatucci A. M., Kaufman T. C., Kennison J. A. brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell. 1992 Feb 7;68(3):561–572. doi: 10.1016/0092-8674(92)90191-e. [DOI] [PubMed] [Google Scholar]
- Tsuji S., Hisaoka M., Morimitsu Y., Hashimoto H., Shimajiri S., Komiya S., Ushijima M., Nakamura T. Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues. Am J Pathol. 1998 Dec;153(6):1807–1812. doi: 10.1016/S0002-9440(10)65695-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turc-Carel C., Dal Cin P., Limon J., Rao U., Li F. P., Corson J. M., Zimmerman R., Parry D. M., Cowan J. M., Sandberg A. A. Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1981–1985. doi: 10.1073/pnas.84.7.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zeren H., Moran C. A., Suster S., Fishback N. F., Koss M. N. Primary pulmonary sarcomas with features of monophasic synovial sarcoma: a clinicopathological, immunohistochemical, and ultrastructural study of 25 cases. Hum Pathol. 1995 May;26(5):474–480. doi: 10.1016/0046-8177(95)90242-2. [DOI] [PubMed] [Google Scholar]
- de Bruijn D. R., Baats E., Zechner U., de Leeuw B., Balemans M., Olde Weghuis D., Hirning-Folz U., Geurts van Kessel A. G. Isolation and characterization of the mouse homolog of SYT, a gene implicated in the development of human synovial sarcomas. Oncogene. 1996 Aug 1;13(3):643–648. [PubMed] [Google Scholar]
- de Leeuw B., Balemans M., Geurts van Kessel A. 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. Cytogenet Cell Genet. 1996;73(3):179–183. doi: 10.1159/000134334. [DOI] [PubMed] [Google Scholar]
- dos Santos N. R., de Bruijn D. R., Balemans M., Janssen B., Gärtner F., Lopes J. M., de Leeuw B., Geurts van Kessel A. Nuclear localization of SYT, SSX and the synovial sarcoma-associated SYT-SSX fusion proteins. Hum Mol Genet. 1997 Sep;6(9):1549–1558. doi: 10.1093/hmg/6.9.1549. [DOI] [PubMed] [Google Scholar]