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. 1995 May 15;14(10):2333–2340. doi: 10.1002/j.1460-2075.1995.tb07228.x

Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma.

A J Crew 1, J Clark 1, C Fisher 1, S Gill 1, R Grimer 1, A Chand 1, J Shipley 1, B A Gusterson 1, C S Cooper 1
PMCID: PMC398342  PMID: 7539744

Abstract

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 Xp11.2. 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. PCR analysis demonstrates the presence of SYT-SSX1 or SYT-SSX2 fusion transcripts in 29 of 32 of the synovial sarcomas examined, indicating that the detection of these hybrid transcripts by PCR may represent a very useful diagnostic method. Sequence analysis has demonstrated heterogeneity in the fusion transcripts with the formation of two distinct SYT-SSX1 fusion junctions and two distinct SYT-SSX2 fusion junctions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aman P., Ron D., Mandahl N., Fioretos T., Heim S., Arheden K., Willén H., Rydholm A., Mitelman F. Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes Chromosomes Cancer. 1992 Nov;5(4):278–285. doi: 10.1002/gcc.2870050403. [DOI] [PubMed] [Google Scholar]
  2. Barr F. G., Galili N., Holick J., Biegel J. A., Rovera G., Emanuel B. S. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Feb;3(2):113–117. doi: 10.1038/ng0293-113. [DOI] [PubMed] [Google Scholar]
  3. Bellefroid E. J., Poncelet D. A., Lecocq P. J., Revelant O., Martial J. A. The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3608–3612. doi: 10.1073/pnas.88.9.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  5. Clark J., Rocques P. J., Crew A. J., Gill S., Shipley J., Chan A. M., 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. Nat Genet. 1994 Aug;7(4):502–508. doi: 10.1038/ng0894-502. [DOI] [PubMed] [Google Scholar]
  6. Cooper C. S., Stratton M. R. Soft tissue tumours: the genetic basis of development. Carcinogenesis. 1991 Feb;12(2):155–165. doi: 10.1093/carcin/12.2.155. [DOI] [PubMed] [Google Scholar]
  7. Cooper C. S. The molecular and genetic characterization of human soft tissue tumors. Adv Cancer Res. 1993;60:75–120. doi: 10.1016/s0065-230x(08)60823-4. [DOI] [PubMed] [Google Scholar]
  8. Crozat A., Aman P., Mandahl N., Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993 Jun 17;363(6430):640–644. doi: 10.1038/363640a0. [DOI] [PubMed] [Google Scholar]
  9. Davis R. J., D'Cruz C. M., Lovell M. A., Biegel J. A., Barr F. G. Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma. Cancer Res. 1994 Jun 1;54(11):2869–2872. [PubMed] [Google Scholar]
  10. Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., Kovar H., Joubert I., de Jong P., Rouleau G. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992 Sep 10;359(6391):162–165. doi: 10.1038/359162a0. [DOI] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Galili N., Davis R. J., Fredericks W. J., Mukhopadhyay S., Rauscher F. J., 3rd, Emanuel B. S., Rovera G., Barr F. G. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Nov;5(3):230–235. doi: 10.1038/ng1193-230. [DOI] [PubMed] [Google Scholar]
  14. Knight J. C., Reeves B. R., Kearney L., Monaco A. P., Lehrach H., Cooper C. S. Localization of the synovial sarcoma t(X;18)(p11.2;q11.2) breakpoint by fluorescence in situ hybridization. Hum Mol Genet. 1992 Nov;1(8):633–637. doi: 10.1093/hmg/1.8.633. [DOI] [PubMed] [Google Scholar]
  15. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kruger W., Herskowitz I. A negative regulator of HO transcription, SIN1 (SPT2), is a nonspecific DNA-binding protein related to HMG1. Mol Cell Biol. 1991 Aug;11(8):4135–4146. doi: 10.1128/mcb.11.8.4135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Licht J. D., Ro M., English M. A., Grossel M., Hansen U. Selective repression of transcriptional activators at a distance by the Drosophila Krüppel protein. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11361–11365. doi: 10.1073/pnas.90.23.11361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Limon J., Mrozek K., Mandahl N., Nedoszytko B., Verhest A., Rys J., Niezabitowski A., Babinska M., Nosek H., Ochalek T. Cytogenetics of synovial sarcoma: presentation of ten new cases and review of the literature. Genes Chromosomes Cancer. 1991 Sep;3(5):338–345. doi: 10.1002/gcc.2870030504. [DOI] [PubMed] [Google Scholar]
  19. Margolin J. F., Friedman J. R., Meyer W. K., Vissing H., Thiesen H. J., Rauscher F. J., 3rd Krüppel-associated boxes are potent transcriptional repression domains. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4509–4513. doi: 10.1073/pnas.91.10.4509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. May W. A., Gishizky M. L., Lessnick S. L., Lunsford L. B., Lewis B. C., Delattre O., Zucman J., Thomas G., Denny C. T. Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5752–5756. doi: 10.1073/pnas.90.12.5752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mitchell P. J., Cooper C. S. Nucleotide sequence analysis of human tpr cDNA clones. Oncogene. 1992 Feb;7(2):383–388. [PubMed] [Google Scholar]
  22. Mitchell P. J., Cooper C. S. The human tpr gene encodes a protein of 2094 amino acids that has extensive coiled-coil regions and an acidic C-terminal domain. Oncogene. 1992 Nov;7(11):2329–2333. [PubMed] [Google Scholar]
  23. Nojima T., Wang Y. S., Abe S., Matsuno T., Yamawaki S., Nagashima K. Morphological and cytogenetic studies of a human synovial sarcoma xenotransplanted into nude mice. Acta Pathol Jpn. 1990 Jul;40(7):486–493. doi: 10.1111/j.1440-1827.1990.tb01590.x. [DOI] [PubMed] [Google Scholar]
  24. Rabbitts T. H. Chromosomal translocations in human cancer. Nature. 1994 Nov 10;372(6502):143–149. doi: 10.1038/372143a0. [DOI] [PubMed] [Google Scholar]
  25. Rabbitts T. H., Forster A., Larson R., Nathan P. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet. 1993 Jun;4(2):175–180. doi: 10.1038/ng0693-175. [DOI] [PubMed] [Google Scholar]
  26. Reeves B. R., Smith S., Fisher C., Warren W., Knight J., Martin C., Chan A. M., Gusterson B. A., Westbury G., Cooper C. S. Characterization of the translocation between chromosomes X and 18 in human synovial sarcomas. Oncogene. 1989 Mar;4(3):373–378. [PubMed] [Google Scholar]
  27. Ron D., Habener J. F. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 1992 Mar;6(3):439–453. doi: 10.1101/gad.6.3.439. [DOI] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sekiguchi T., Nohiro Y., Nakamura Y., Hisamoto N., Nishimoto T. The human CCG1 gene, essential for progression of the G1 phase, encodes a 210-kilodalton nuclear DNA-binding protein. Mol Cell Biol. 1991 Jun;11(6):3317–3325. doi: 10.1128/mcb.11.6.3317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shipley J. M., Clark J., Crew A. J., Birdsall S., Rocques P. J., Gill S., Chelly J., Monaco A. P., Abe S., Gusterson B. A. The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome. Oncogene. 1994 May;9(5):1447–1453. [PubMed] [Google Scholar]
  31. Shirakawa H., Tsuda K., Yoshida M. Primary structure of non-histone chromosomal protein HMG2 revealed by the nucleotide sequence. Biochemistry. 1990 May 8;29(18):4419–4423. doi: 10.1021/bi00470a022. [DOI] [PubMed] [Google Scholar]
  32. Smith S., Reeves B. R., Wong L., Fisher C. A consistent chromosome translocation in synovial sarcoma. Cancer Genet Cytogenet. 1987 May;26(1):179–180. doi: 10.1016/0165-4608(87)90147-6. [DOI] [PubMed] [Google Scholar]
  33. Sonobe H., Manabe Y., Furihata M., Iwata J., Oka T., Ohtsuki Y., Mizobuchi H., Yamamoto H., Kumano O., Abe S. Establishment and characterization of a new human synovial sarcoma cell line, HS-SY-II. Lab Invest. 1992 Oct;67(4):498–505. [PubMed] [Google Scholar]
  34. Sorensen P. H., Lessnick S. L., Lopez-Terrada D., Liu X. F., Triche T. J., Denny C. T. A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet. 1994 Feb;6(2):146–151. doi: 10.1038/ng0294-146. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Wang-Wuu S., Soukup S. W., Lange B. J. Another synovial sarcoma with t(X;18) Cancer Genet Cytogenet. 1987 Nov;29(1):179–181. doi: 10.1016/0165-4608(87)90048-3. [DOI] [PubMed] [Google Scholar]
  37. Witzgall R., O'Leary E., Leaf A., Onaldi D., Bonventre J. V. The Krüppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4514–4518. doi: 10.1073/pnas.91.10.4514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zucman J., Melot T., Desmaze C., Ghysdael J., Plougastel B., Peter M., Zucker J. M., Triche T. J., Sheer D., Turc-Carel C. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J. 1993 Dec;12(12):4481–4487. doi: 10.1002/j.1460-2075.1993.tb06137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. de Leeuw B., Berger W., Sinke R. J., Suijkerbuijk R. F., Gilgenkrantz S., Geraghty M. T., Valle D., Monaco A. P., Lehrach H., Ropers H. H. Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18)(p11.2;q11.2) breakpoint. Genes Chromosomes Cancer. 1993 Mar;6(3):182–189. doi: 10.1002/gcc.2870060309. [DOI] [PubMed] [Google Scholar]
  40. de Leeuw B., Suijkerbuijk R. F., Olde Weghuis D., Meloni A. M., Stenman G., Kindblom L. G., Balemans M., van den Berg E., Molenaar W. M., Sandberg A. A. Distinct Xp11.2 breakpoint regions in synovial sarcoma revealed by metaphase and interphase FISH: relationship to histologic subtypes. Cancer Genet Cytogenet. 1994 Apr;73(2):89–94. doi: 10.1016/0165-4608(94)90191-0. [DOI] [PubMed] [Google Scholar]

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