title: The SYT-SSX1 fusion type of synovial sarcoma is associated with increased expression of cyclin A and D1. A link between t(X;18)(p11.2; q11.2) and the cell cycle machinery.
abstract: 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.
authors.affiliation: Department of Oncology and Pathology, CCK R8: 04, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
authors.forename: Bjorn
authors.initials: B
authors.lastname: Skytting
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Grimer
authors.forename: Chas D
authors.initials: CD
authors.lastname: Mangham
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjerkehagen
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
authors.forename: Olle
authors.initials: O
authors.lastname: Larsson
mesh_terms: D002453:Cell Cycle; D002887:Chromosomes, Human, Pair 18; D019925:Cyclin A / Q000032:analysis*; D019938:Cyclin D1 / Q000032:analysis*; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013584:Sarcoma, Synovial / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D019925:Cyclin A; D015514:Oncogene Proteins, Fusion; D019253:Proto-Oncogene Proteins c-bcl-2; C116512:SYT-SSX fusion protein; D019938:Cyclin D1