1Department of Oncology and Pathology, CCK R8: 04, Karolinska Hospital, Stockholm, Sweden
2Department of Oncology, Zhongnan Hospital, Wuhan University, Wuhan, PR China
3Department of Orthopedics, Stockholm Soder Hospital, Stockholm, Sweden
4Department of Orthopedics, Karolinska Hospital, Stockholm, Sweden
5Royal Orthopaedic Hospital, Northfield, Birmingham, UK
6Department of Pathology, the Royal Marsden NHS Trust, London, UK
7Molecular Cytogenetics Team, Institute of Cancer Research, Sutton, UK
8Department of Pathology, nstitute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
9Department of Tumour Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
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A recent large multi-centre study convincingly confirmed previous observations that the SYT-SSX1 fusion type, compared to SYT-SSX2, of synovial sarcoma is associated with a worse clinical outcome. Apart from the clinical impact, this fact also suggests (1) that the SYT-SSX fusion gene may influence molecular mechanisms involved in tumour growth and progression; and (2) that the SYT-SSX1 fusion type has a stronger influence on these mechanisms than SYT-SSX2. The nature of the underlying mechanisms is, however, still unknown. In this study we made use of the SYT-SSX1 vs SYT-SSX2 concept to investigate whether major, tumour relevant, and growth regulatory proteins (e.g. cyclins and cyclin-dependent kinases) may be involved. Using Western blotting analysis on 74 fresh, fusion variant-typed, tumour samples from localized synovial sarcoma, we found a significant correlation between SYT-SSX1 and high expression of cyclin A (P=0.003) and D1 (P=0.025). Our data suggest that SYT-SSX may influence the cell cycle machinery, and that the more aggressive phenotype of the SYT-SSX1 variant is due to an accelerated tumour cell proliferation. Oncogene (2002) 21, 5791-5796. doi:10.1038/sj.onc.1205700 |
