Skip to main content

Advertisement

SpringerLink
Log in

Synovial Sarcoma: From Genetics to Genetic-based Animal Modeling

  • Symposium: Molecular Genetics in Sarcoma
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Synovial sarcomas are highly aggressive mesenchymal cancers that show modest response to conventional cytotoxic chemotherapy, suggesting a definite need for improved biotargeted agents. Progress has been hampered by the lack of insight into pathogenesis of this deadly disease. The presence of a specific diagnostic t(X;18) translocation leading to expression of the unique SYT-SSX fusion protein in effectively all cases of synovial sarcoma suggests a role in the etiology. Other nonspecific anomalies such as overexpression of Bcl-2, HER-2/neu, and EGFR have been reported, but their role in the pathogenesis remains unclear. Using gene targeting, we recently generated mice conditionally expressing the human SYT-SSX2 fusion gene from mouse endogenous ROSA26 promoter in chosen tissue types in the presence of Cre recombinase. These mice develop synovial sarcoma when SYT-SSX2 is expressed within myoblasts, thereby identifying a source of this enigmatic tumor and establishing a mouse model of this disease that recapitulates the clinical, histologic, immunohistochemical, and transcriptional profile of human synovial sarcomas. We review the genetics of synovial sarcoma and discuss the usefulness of genetics-based mouse models as a valuable research tool in the hunt for key molecular determinants of this lethal disease as well as a preclinical platform for designing and evaluating novel treatment strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A−C
Fig. 2
Fig. 3A–F

Similar content being viewed by others

References

  1. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet. 1997;350:1647–1654.

  2. Allander SV, Illei PB, Chen Y, Antonescu CR, Bittner M, Ladanyi M, Meltzer PS. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol. 2002;161:1587–1595.

    PubMed  CAS  Google Scholar 

  3. Antonescu CR, Kawai A, Leung DH, Lonardo F, Woodruff JM, Healey JH, Ladanyi M. Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma. Diagn Mol Pathol. 2000;9:1–8.

    Article  PubMed  CAS  Google Scholar 

  4. Barco R, Hunt LB, Frump AL, Garcia CB, Benesh A, Caldwell RL, Eid JE. The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway. Mol Biol Cell. 2007;18:4003–4012.

    Article  PubMed  CAS  Google Scholar 

  5. Birdsall S, Osin P, Lu YJ, Fisher C, Shipley J. Synovial sarcoma specific translocation associated with both epithelial and spindle cell components. Int J Cancer. 1999;82:605–608.

    Article  PubMed  CAS  Google Scholar 

  6. Blay JY, Ray-Coquard I, Alberti L, Ranchere D. Targeting other abnormal signaling pathways in sarcoma: EGFR in synovial sarcomas, PPAR-gamma in liposarcomas. Cancer Treat Res. 2004;120:151–167.

    Article  PubMed  CAS  Google Scholar 

  7. 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;6:1559–1564.

    Article  PubMed  CAS  Google Scholar 

  8. Capecchi MR. Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet. 2005;6:507–512.

    Article  PubMed  CAS  Google Scholar 

  9. Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM, Gusterson BA, Cooper CS. 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;7:502–508.

    Article  PubMed  CAS  Google Scholar 

  10. Crew AJ, Clark J, Fisher C, Gill S, Grimer R, Chand A, Shipley J, Gusterson BA, Cooper CS. 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;14:2333–2340.

    PubMed  CAS  Google Scholar 

  11. de Bruijn DR, dos Santos NR, Thijssen J, Balemans M, Debernardi S, Linder B, Young BD, Geurts van Kessel A. The synovial sarcoma associated protein SYT interacts with the acute leukemia associated protein AF10. Oncogene. 2001;20:3281–3289.

    Article  PubMed  CAS  Google Scholar 

  12. de Bruijn DR, Kater-Baats E, Eleveld M, Merkx G, Geurts Van Kessel A. Mapping and characterization of the mouse and human SS18 genes, two human SS18-like genes and a mouse Ss18 pseudogene. Cytogenet Cell Genet. 2001;92:310–319.

    Article  PubMed  Google Scholar 

  13. de Bruijn DR, Peters WJ, Chuva de Sousa Lopes SM, van Dijk AH, Willemse MP, Pfundt R, de Boer P, Geurts van Kessel A. Targeted disruption of the synovial sarcoma-associated SS18 gene causes early embryonic lethality and affects PPARBP expression. Hum Mol Genet. 2006;15:2936–2944.

    Article  PubMed  CAS  Google Scholar 

  14. de Bruijn DR, Peters WJ, de Sousa Lopes SM, van Dijk AH, Willemse MP, Pfundt R, de Boer P, van Kessel AG. Targeted disruption of the synovial sarcoma-associated SS18 gene causes early embryonic lethality and affects PPARBP expression. Hum Mol Genet. 2006;15:2936–2944.

    Article  PubMed  CAS  Google Scholar 

  15. de Bruijn DR, van Dijk AH, Willemse MP, van Kessel AG. The C terminus of the synovial sarcoma-associated SSX proteins interacts with the LIM homeobox protein LHX4. Oncogene. 2008;27:653–662.

    Article  PubMed  CAS  Google Scholar 

  16. de Leeuw B, Balemans M, Olde Weghuis D, Geurts van Kessel A. Identification of two alternative fusion genes, SYT-SSX1 and SYT-SSX2, in t(X;18)(p11.2;q11.2)-positive synovial sarcomas. Hum Mol Genet. 1995;4:1097–1099.

    Article  PubMed  Google Scholar 

  17. Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992;359:162–165.

    Article  PubMed  CAS  Google Scholar 

  18. dos Santos NR, de Bruijn DR, Kater-Baats E, Otte AP, van Kessel AG. Delineation of the protein domains responsible for SYT, SSX, and SYT-SSX nuclear localization. Exp Cell Res. 2000;256:192–202.

    Article  PubMed  CAS  Google Scholar 

  19. dos Santos NR, de Bruijn DR, van Kessel AG. Molecular mechanisms underlying human synovial sarcoma development. Genes Chromosomes Cancer. 2001;30:1–14.

    Article  PubMed  CAS  Google Scholar 

  20. Eid JE, Kung AL, Scully R, Livingston DM. p300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion. Cell. 2000;102:839–848.

    Article  PubMed  CAS  Google Scholar 

  21. Fernebro J, Francis P, Eden P, Borg A, Panagopoulos I, Mertens F, Vallon-Christersson J, Akerman M, Rydholm A, Bauer HC, Mandahl N, Nilbert M. Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma. Int J Cancer. 2006;118:1165–1172.

    Article  PubMed  CAS  Google Scholar 

  22. Ferrari A, Gronchi A, Casanova M, Meazza C, Gandola L, Collini P, Lozza L, Bertulli R, Olmi P, Casali PG. Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution. Cancer. 2004;101:627–634.

    Article  PubMed  Google Scholar 

  23. Folpe AL, Schmidt RA, Chapman D, Gown AM. Poorly differentiated synovial sarcoma: immunohistochemical distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath tumors. Am J Surg Pathol. 1998;22:673–682.

    Article  PubMed  CAS  Google Scholar 

  24. Fukukawa C, Nakamura Y, Katagiri T. Molecular target therapy for synovial sarcoma. Future Oncol. 2005;1:805–812.

    Article  PubMed  CAS  Google Scholar 

  25. Guillou L, Benhattar J, Bonichon F, Gallagher G, Terrier P, Stauffer E, Somerhausen Nde S, Michels JJ, Jundt G, Vince DR, Taylor S, Genevay M, Collin F, Trassard M, Coindre JM. Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis. J Clin Oncol. 2004;22:4040–4050.

    Article  PubMed  Google Scholar 

  26. Gure AO, Tureci O, Sahin U, Tsang S, Scanlan MJ, Jager E, Knuth A, Pfreundschuh M, Old LJ, Chen YT. SSX: a multigene family with several members transcribed in normal testis and human cancer. Int J Cancer. 1997;72:965–971.

    Article  PubMed  CAS  Google Scholar 

  27. Gure AO, Wei IJ, Old LJ, Chen YT. The SSX gene family: characterization of 9 complete genes. Int J Cancer. 2002;101:448–453.

    Article  PubMed  CAS  Google Scholar 

  28. Haldar M, Hancock JD, Coffin CM, Lessnick SL, Capecchi MR. A conditional mouse model of synovial sarcoma: insights into a myogenic origin. Cancer Cell. 2007;11:375–388.

    Article  PubMed  CAS  Google Scholar 

  29. Hibshoosh H, Lattes R. Immunohistochemical and molecular genetic approaches to soft tissue tumor diagnosis: a primer. Semin Oncol. 1997;24:515–525.

    PubMed  CAS  Google Scholar 

  30. Hiraga H, Nojima T, Abe S, Sawa H, Yamashiro K, Yamawaki S, Kaneda K, Nagashima K. Diagnosis of synovial sarcoma with the reverse transcriptase-polymerase chain reaction: analyses of 84 soft tissue and bone tumors. Diagn Mol Pathol. 1998;7:102–110.

    Article  PubMed  CAS  Google Scholar 

  31. Ishida M, Tanaka S, Ohki M, Ohta T. Transcriptional co-activator activity of SYT is negatively regulated by BRM and Brg1. Genes Cells. 2004;9:419–428.

    Article  PubMed  CAS  Google Scholar 

  32. Ito T, Ouchida M, Ito S, Jitsumori Y, Morimoto Y, Ozaki T, Kawai A, Inoue H, Shimizu K. SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with mSin3A, a component of histone deacetylase complex. Lab Invest. 2004;84:1484–1490.

    Article  PubMed  CAS  Google Scholar 

  33. Joyner DE, Albritton KH, Bastar JD, Randall RL. G3139 antisense oligonucleotide directed against antiapoptotic Bcl-2 enhances doxorubicin cytotoxicity in the FU-SY-1 synovial sarcoma cell line. J Orthop Res. 2006;24:474–480.

    Article  PubMed  CAS  Google Scholar 

  34. Kasai T, Shimajiri S, Hashimoto H. Detection of SYT-SSX fusion transcripts in both epithelial and spindle cell areas of biphasic synovial sarcoma using laser capture microdissection. Mol Pathol. 2000;53:107–110.

    Article  PubMed  CAS  Google Scholar 

  35. Kato H, Tjernberg A, Zhang W, Krutchinsky AN, An W, Takeuchi T, Ohtsuki Y, Sugano S, de Bruijn DR, Chait BT, Roeder RG. SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones. J Biol Chem. 2002;277:5498–5505.

    Article  PubMed  CAS  Google Scholar 

  36. Kawaguchi S, Wada T, Ida K, Sato Y, Nagoya S, Tsukahara T, Kimura S, Sahara H, Ikeda H, Shimozawa K, Asanuma H, Torigoe T, Hiraga H, Ishii T, Tatezaki SI, Sato N, Yamashita T. Phase I vaccination trial of SYT-SSX junction peptide in patients with disseminated synovial sarcoma. J Transl Med. 2005;3:1.

    Article  PubMed  CAS  Google Scholar 

  37. Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med. 1998;338:153–160.

    Article  PubMed  CAS  Google Scholar 

  38. Koch CA, Anderson D, Moran MF, Ellis C, Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991;252:668–674.

    Article  PubMed  CAS  Google Scholar 

  39. Ladanyi M, Antonescu CR, Leung DH, Woodruff JM, Kawai A, Healey JH, Brennan MF, Bridge JA, Neff JR, Barr FG, Goldsmith JD, Brooks JS, Goldblum JR, Ali SZ, Shipley J, Cooper CS, 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. 2002;62:135–140.

    PubMed  CAS  Google Scholar 

  40. Lewis JJ, Antonescu CR, Leung DH, Blumberg D, Healey JH, Woodruff JM, Brennan MF. Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol. 2000;18:2087–2094.

    PubMed  CAS  Google Scholar 

  41. Lim FL, Soulez M, Koczan D, Thiesen HJ, Knight JC. A KRAB-related domain and a novel transcription repression domain in proteins encoded by SSX genes that are disrupted in human sarcomas. Oncogene. 1998;17:2013–2018.

    Article  PubMed  CAS  Google Scholar 

  42. Llombart-Bosch A, Lopez-Guerrero JA, Peydro-Olaya A. Synovial sarcoma (SS): new perspectives supported by modern technology. Arkh Patol. 2002;64:39–47.

    PubMed  CAS  Google Scholar 

  43. Lopes JM, Nesland JM, Reis-Filho JS, Holm R. Differential Ki67 and bcl-2 immunoexpression in solid-glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin. Histopathology. 2002;40:464–471.

    Article  PubMed  CAS  Google Scholar 

  44. Mancuso T, Mezzelani A, Riva C, Fabbri A, Dal Bo L, Sampietro G, Perego P, Casali P, Zunino F, Sozzi G, Pierotti MA, Pilotti S. Analysis of SYT-SSX fusion transcripts and bcl-2 expression and phosphorylation status in synovial sarcoma. Lab Invest. 2000;80:805–813.

    PubMed  CAS  Google Scholar 

  45. Margolin JF, Friedman JR, Meyer WK, Vissing H, Thiesen HJ, Rauscher FJ 3rd. Kruppel-associated boxes are potent transcriptional repression domains. Proc Natl Acad Sci USA. 1994;91:4509–4513.

    Article  PubMed  CAS  Google Scholar 

  46. Miettinen M, Virtanen I. Synovial sarcoma—a misnomer. Am J Pathol. 1984;117:18–25.

    PubMed  CAS  Google Scholar 

  47. Motoi T, Ishida T, Kuroda M, Horiuchi H, Oka T, Matsumoto K, Nakamura T, Machinami R. Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma. Pathol Int. 1998;48:769–775.

    Article  PubMed  CAS  Google Scholar 

  48. Mullen JR, Zagars GK. Synovial sarcoma outcome following conservation surgery and radiotherapy. Radiother Oncol. 1994;33:23–30.

    Article  PubMed  CAS  Google Scholar 

  49. Nagai M, Tanaka S, Tsuda M, Endo S, Kato H, Sonobe H, Minami A, Hiraga H, Nishihara H, Sawa H, Nagashima K. Analysis of transforming activity of human synovial sarcoma-associated chimeric protein SYT-SSX1 bound to chromatin remodeling factor hBRM/hSNF2 alpha. Proc Natl Acad Sci USA. 2001;98:3843–3848.

    Article  PubMed  CAS  Google Scholar 

  50. Nagayama S, Katagiri T, Tsunoda T, Hosaka T, Nakashima Y, Araki N, Kusuzaki K, Nakayama T, Tsuboyama T, Nakamura T, Imamura M, Nakamura Y, Toguchida J. Genome-wide analysis of gene expression in synovial sarcomas using a cDNA microarray. Cancer Res. 2002;62:5859–5866.

    PubMed  CAS  Google Scholar 

  51. Nielsen TO, Hsu FD, O’Connell JX, Gilks CB, Sorensen PH, Linn S, West RB, Liu CL, Botstein D, Brown PO, van de Rijn M. Tissue microarray validation of epidermal growth factor receptor and SALL2 in synovial sarcoma with comparison to tumors of similar histology. Am J Pathol. 2003;163:1449–1456.

    PubMed  CAS  Google Scholar 

  52. Nielsen TO, West RB, Linn SC, Alter O, Knowling MA, O’Connell JX, Zhu S, Fero M, Sherlock G, Pollack JR, Brown PO, Botstein D, van de Rijn M. Molecular characterisation of soft tissue tumours: a gene expression study. Lancet. 2002;359:1301–1307.

    Article  PubMed  CAS  Google Scholar 

  53. Nilsson G, Skytting B, Xie Y, Brodin B, Perfekt R, Mandahl N, Lundeberg J, Uhlen M, Larsson O. The SYT-SSX1 variant of synovial sarcoma is associated with a high rate of tumor cell proliferation and poor clinical outcome. Cancer Res. 1999;59:3180–3184.

    PubMed  CAS  Google Scholar 

  54. O’Byrne K, Steward WP. The role of chemotherapy in the treatment of adult soft tissue sarcomas. Oncology. 1999;56:13–23.

    Article  PubMed  CAS  Google Scholar 

  55. Oda Y, Sakamoto A, Satio T, Kawauchi S, Iwamoto Y, Tsuneyoshi M. Molecular abnormalities of p53, MDM2, and H-ras in synovial sarcoma. Mod Pathol. 2000;13:994–1004.

    Article  PubMed  CAS  Google Scholar 

  56. Panagopoulos I, Mertens F, Isaksson M, Limon J, Gustafson P, Skytting B, Akerman M, Sciot R, Dal Cin P, Samson I, Iliszko M, Ryoe J, Debiec-Rychter M, Szadowska A, Brosjo O, Larsson O, Rydholm A, Mandahl N. Clinical impact of molecular and cytogenetic findings in synovial sarcoma. Genes Chromosomes Cancer. 2001;31:362–372.

    Article  PubMed  CAS  Google Scholar 

  57. Paulino AC. Synovial sarcoma prognostic factors and patterns of failure. Am J Clin Oncol. 2004;27:122–127.

    Article  PubMed  Google Scholar 

  58. Pawson T, Gish GD. SH2 and SH3 domains: from structure to function. Cell. 1992;71:359–362.

    Article  PubMed  CAS  Google Scholar 

  59. Pelmus M, Guillou L, Hostein I, Sierankowski G, Lussan C, Coindre JM. Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. Am J Surg Pathol. 2002;26:1434–1440.

    Article  PubMed  Google Scholar 

  60. Perani M, Ingram CJ, Cooper CS, Garrett MD, Goodwin GH. Conserved SNH domain of the proto-oncoprotein SYT interacts with components of the human chromatin remodelling complexes, while the QPGY repeat domain forms homo-oligomers. Oncogene. 2003;22:8156–8167.

    Article  PubMed  CAS  Google Scholar 

  61. Pisters PW, Patel SR, Prieto VG, Thall PF, Lewis VO, Feig BW, Hunt KK, Yasko AW, Lin PP, Jacobson MG, Burgess MA, Pollock RE, Zagars GK, Benjamin RS, Ballo MT. Phase I trial of preoperative doxorubicin-based concurrent chemoradiation and surgical resection for localized extremity and body wall soft tissue sarcomas. J Clin Oncol. 2004;22:3375–3380.

    Article  PubMed  CAS  Google Scholar 

  62. Pretto D, Barco R, Rivera J, Neel N, Gustavson MD, Eid JE. The synovial sarcoma translocation protein SYT-SSX2 recruits beta-catenin to the nucleus and associates with it in an active complex. Oncogene. 2006;25:3661–3669.

    Article  PubMed  CAS  Google Scholar 

  63. Rosenberg SA. Prospective randomized trials demonstrating the efficacy of adjuvant chemotherapy in adult patients with soft tissue sarcomas. Cancer Treat Rep. 1984;68:1067–1078.

    PubMed  CAS  Google Scholar 

  64. Saito T, Nagai M, Ladanyi M. 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. Cancer Res. 2006;66:6919–6927.

    Article  PubMed  CAS  Google Scholar 

  65. Saito T, Oda Y, Kawaguchi K, Takahira T, Yamamoto H, Tanaka K, Matsuda S, Sakamoto A, Iwamoto Y, Tsuneyoshi M. PTEN and other tumor suppressor gene mutations as secondary genetic alterations in synovial sarcoma. Oncol Rep. 2004;11:1011–1015.

    PubMed  CAS  Google Scholar 

  66. Saito T, Oda Y, Sakamoto A, Kawaguchi K, Tanaka K, Matsuda S, Tamiya S, Iwamoto Y, Tsuneyoshi M. APC mutations in synovial sarcoma. J Pathol. 2002;196:445–449.

    Article  PubMed  CAS  Google Scholar 

  67. Sato Y, Nabeta Y, Tsukahara T, Hirohashi Y, Syunsui R, Maeda A, Sahara H, Ikeda H, Torigoe T, Ichimiya S, Wada T, Yamashita T, Hiraga H, Kawai A, Ishii T, Araki N, Myoui A, Matsumoto S, Umeda T, Ishii S, Kawaguchi S, Sato N. Detection and induction of CTLs specific for SYT-SSX-derived peptides in HLA-A24(+) patients with synovial sarcoma. J Immunol. 2002;169:1611–1618.

    PubMed  CAS  Google Scholar 

  68. Sauer B, Henderson N. Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome. Nucleic Acids Res. 1989;17:147–161.

    Article  PubMed  CAS  Google Scholar 

  69. Shipley JM, Clark J, Crew AJ, Birdsall S, Rocques PJ, Gill S, Chelly J, Monaco AP, Abe S, Gusterson BA, et al. The t(X;18)(p11.2;q11.2) translocation found in human synovial sarcomas involves two distinct loci on the X chromosome. Oncogene. 1994;9:1447–1453.

    PubMed  CAS  Google Scholar 

  70. Skytting B, Nilsson G, Brodin B, Xie Y, Lundeberg J, Uhlen M, Larsson O. A novel fusion gene, SYT-SSX4, in synovial sarcoma. J Natl Cancer Inst. 1999;91:974–975.

    Article  PubMed  CAS  Google Scholar 

  71. Smith ME, Fisher C, Wilkinson LS, Edwards JC. Synovial sarcoma lack synovial differentiation. Histopathology. 1995;26:279–281.

    Article  PubMed  CAS  Google Scholar 

  72. Smith S, Reeves BR, Wong L, Fisher C. A consistent chromosome translocation in synovial sarcoma. Cancer Genet Cytogenet. 1987;26:179–180.

    Article  PubMed  CAS  Google Scholar 

  73. Soulez M, Saurin AJ, Freemont PS, Knight JC. SSX and the synovial-sarcoma-specific chimaeric protein SYT-SSX co-localize with the human Polycomb group complex. Oncogene. 1999;18:2739–2746.

    Article  PubMed  CAS  Google Scholar 

  74. Spillane AJ, A’Hern R, Judson IR, Fisher C, Thomas JM. Synovial sarcoma: a clinicopathologic, staging, and prognostic assessment. J Clin Oncol. 2000;18:3794–3803.

    PubMed  CAS  Google Scholar 

  75. Spurrell EL, Fisher C, Thomas JM, Judson IR. Prognostic factors in advanced synovial sarcoma: an analysis of 104 patients treated at the Royal Marsden Hospital. Ann Oncol. 2005;16:437–444.

    Article  PubMed  CAS  Google Scholar 

  76. Sun Y, Gao D, Liu Y, Huang J, Lessnick S, Tanaka S. IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1. Oncogene. 2006;25:1042–1052.

    Article  PubMed  CAS  Google Scholar 

  77. Tamborini E, Bonadiman L, Greco A, Gronchi A, Riva C, Bertulli R, Casali PG, Pierotti MA, Pilotti S. Expression of ligand-activated KIT and platelet-derived growth factor receptor beta tyrosine kinase receptors in synovial sarcoma. Clin Cancer Res. 2004;10:938–943.

    Article  PubMed  CAS  Google Scholar 

  78. Terry J, Saito T, Subramanian S, Ruttan C, Antonescu CR, Goldblum JR, Downs-Kelly E, Corless CL, Rubin BP, van de Rijn M, Ladanyi M, Nielsen TO. TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. Am J Surg Pathol. 2007;31:240–246.

    Article  PubMed  Google Scholar 

  79. Thaete C, Brett D, Monaghan P, Whitehouse S, Rennie G, Rayner E, Cooper CS, Goodwin G. Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus. Hum Mol Genet. 1999;8:585–591.

    Article  PubMed  CAS  Google Scholar 

  80. Tureci O, Chen YT, Sahin U, Gure AO, Zwick C, Villena C, Tsang S, Seitz G, Old LJ, Pfreundschuh M. Expression of SSX genes in human tumors. Int J Cancer. 1998;77:19–23.

    Article  PubMed  CAS  Google Scholar 

  81. van de Rijn M, Barr FG, Collins MH, Xiong QB, Fisher C. Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma. Am J Clin Pathol. 1999;112:43–49.

    PubMed  Google Scholar 

  82. Watanabe T, Tsuda M, Makino Y, Ichihara S, Sawa H, Minami A, Mochizuki N, Nagashima K, Tanaka S. Adaptor molecule Crk is required for sustained phosphorylation of Grb2-associated binder 1 and hepatocyte growth factor-induced cell motility of human synovial sarcoma cell lines. Mol Cancer Res. 2006;4:499–510.

    Article  PubMed  CAS  Google Scholar 

  83. Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors. 4th Ed. St Louis: Mosby, Inc; 2001.

    Google Scholar 

  84. Xie Y, Skytting B, Nilsson G, Brodin B, Larsson O. Expression of insulin-like growth factor-1 receptor in synovial sarcoma: association with an aggressive phenotype. Cancer Res. 1999;59:3588–3591.

    PubMed  CAS  Google Scholar 

  85. Zambrowicz BP, Imamoto A, Fiering S, Herzenberg LA, Kerr WG, Soriano P. Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA. 1997;94:3789–3794.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human Genetics, University of Utah School of Medicine, 15 North 2030 East, Room 5440, Salt Lake City, UT, 84112-5331, USA

    Malay Haldar PhD & Mario R. Capecchi PhD

  2. Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT, USA

    Malay Haldar PhD & Mario R. Capecchi PhD

  3. Huntsman Cancer Institute Sarcoma Services, University of Utah, Salt Lake City, UT, USA

    R. Lor Randall MD

  4. Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, UT, USA

    R. Lor Randall MD

Authors
  1. Malay Haldar PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Lor Randall MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mario R. Capecchi PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario R. Capecchi PhD.

Additional information

Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

About this article

Cite this article

Haldar, M., Randall, R.L. & Capecchi, M.R. Synovial Sarcoma: From Genetics to Genetic-based Animal Modeling. Clin Orthop Relat Res 466, 2156–2167 (2008). https://doi.org/10.1007/s11999-008-0340-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11999-008-0340-2

Keywords

Search

Navigation