title: Co-existence of SYT-SSX1 and SYT-SSX2 fusions in synovial sarcomas.
abstract: The chromosomal translocation t(X;18)(p11.2;q11.2) is tightly linked to the tumorigenesis of synovial sarcoma. Through this translation the SYT gene on chromosome 18 is fused with a testis/cancer antigen gene on the X chromosome, generating either a SYT-SSX1, SYT-SSX2, or less often a SYT-SSX4 fusion gene. It has been anticipated that the individual synovial sarcoma carries only one of these variants, however, in this study we demonstrated that SYT-SSX1 and SYT-SSX2 co-exist in a significant proportion of the cases. From 121 SYT-SSX positive primary tumors, co-expression of SYT-SSX1 and SYT-SSX2 was seen in 12 cases (10%), which were characterized in further detail both at the RNA, DNA and chromosomal level. In all 12 cases the SYT-SSX1 and SYT-SSX2 fusions resulted in identical SYT-SSX fusion transcripts. However, at the genomic level the translocations were different, and most likely occurred between variable intronic sites in the target genes. By interphase FISH analyses of 10 cases SYT-SSX2 translocations were found to be the most abundant in all but one of the cases, in which SYT-SSX1 was predominating. The findings reveal a new heterogenous feature of synovial sarcoma, accounting for approximately 10% of all cases, which may shed light on the molecular genetic mechanisms behind translocations in general, and on the etiology of synovial sarcoma in particular.
authors.affiliation: Department of Oncology and Pathology, Karolinska Hospital CCK R8:04, SE-171 76 Stockohlm, Sweden.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
authors.forename: Anju
authors.initials: A
authors.lastname: Zhang
authors.forename: Björn
authors.initials: B
authors.lastname: Skytting
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Olle
authors.initials: O
authors.lastname: Larsson
mesh_terms: D019677:Artificial Gene Fusion; D002887:Chromosomes, Human, Pair 18; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins / Q000235:genetics*; D013584:Sarcoma, Synovial / Q000235:genetics*; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C093961:SS18 protein, human; C093962:synovial sarcoma X breakpoint proteins