Disease relevance of SS18

• Fusion of the SS18 and (one of the) SSX genes is a molecular hallmark of human synovial sarcomas [1].
• Fifteen other sarcomas and related tumors were negative for SYT-SSX fusion transcripts [2].
• Tetramer analysis indicated that the increased CTLp frequency to the SYT-SSX was associated with pulmonary metastasis in synovial sarcoma patients (p < 0.03) [3].
• To test independently this iconoclastic claim, a molecular analysis for the detection of the SYT-SSX fusion genes was carried out using archival material of 34 consecutive cases diagnosed as malignant peripheral nerve sheath tumors and treated in our Institute from 1998 to 2000 [4].
• A subset of adult rhabdoid tumors may be a rhabdoid variant of synovial sarcoma, and molecular studies to detect SYT-SSX fusion transcripts are recommended for an accurate diagnosis [5].

High impact information on SS18

• SYT sequences constitute the N-terminal segment of a fusion oncogene product, SYT-SSX, routinely detected in synovial sarcoma, an aggressive human tumor [6].
• p300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion [6].
• Re: A novel fusion gene, SYT-SSX4, in synovial sarcoma [7].
• 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 [8].
• The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species, and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences [9].

Chemical compound and disease context of SS18

• Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma [2].
• In this study, we conducted a reverse transcription-polymerase chain reaction-based assay to detect the SYT-SSX fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens from a series of 32 synovial sarcoma cases including 6 tumors found in unusual anatomical sites [10].
• To investigate the distribution of tumour cells expressing the SYT-SSX fusion gene in biphasic synovial sarcoma, modified reverse transcription polymerase chain reaction (RT-PCR) analysis was performed using microdissected specimens from haematoxylin and eosin stained sections of archival paraffin wax embedded tissues [11].

Biological context of SS18

• Because SS18/SSX fusions do not seem to occur in other tumor types, and because synovial sarcomas may sometimes be difficult to distinguish from other spindle cell tumors, molecular genetic analysis has become established as an important diagnostic tool [12].
• Synovial sarcoma is an aggressive soft tissue tumor that is characterized cytogenetically by the t(X;18)(p11;q11) translocation, resulting in fusion between the SS18 gene on chromosome 18 and one of the SSX genes on the X chromosome [12].
• The SS18 protein functions as a transcriptional coactivator and interacts directly with members of the epigenetic chromatin remodeling and modification machineries [1].
• Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma [13].
• By fluorescence in situ hybridization, the marker chromosomes were shown to contain material from chromosomes X and 20, including the SSX gene cluster on the X chromosome and the SS18L1 gene, which shows strong homology with the SS18 gene, on chromosome 20 [12].

Anatomical context of SS18

• We present evidence that SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells [14].
• Stable transfection of an SYT/SSX4 expression vector into human and murine cell lines correlated with a down-regulation of SYT transcripts [15].
• These two SYT forms were present, although in different amounts, in all human normal tissues examined, including kidney, stomach, lung, colon, liver and synovia [16].
• These antibodies specifically detected both these proteins and the SYT-SSX fusion proteins in transfected COS-1 cell extracts [17].
• Since the SYT speckles do not co-localise with PML-containing bodies (PODs) or spliceosomes it is possible that they represent a novel nuclear structure [18].

Associations of SS18 with chemical compounds

• In addition, SYT acts together with SIP/CoAA in stimulating estrogen and glucocorticoid receptor-dependent transcriptional activation [19].
• The SYT-SSX2 fusion transcripts were detected by a reverse transcription-polymerase chain reaction (RT-PCR) using RNA extracted from formalin-fixed, paraffin-embedded tissue [20].

Regulatory relationships of SS18

• In addition, SYT activates transcription through activator protein-1, suggesting that SYT may function as a general coactivator [21].
• Transcriptional co-activator activity of SYT is negatively regulated by BRM and Brg1 [22].

Other interactions of SS18

• The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome [9].
• This translocation can generate a fusion transcript encoding SYT-SSX1, a transforming oncoprotein [14].
• The synovial sarcoma associated protein SYT interacts with the acute leukemia associated protein AF10 [23].
• IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1 [14].
• This was also observed in a synovial sarcoma tumor expressing SYT/SSX4 [15].

Analytical, diagnostic and therapeutic context of SS18

• RT-PCR analysis and sequence analysis demonstrated the presence of SS18/SSX2 fusion gene [24].
• In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes [25].
• The PCR products were confirmed as SYT-SSX sequences by sequencing in five randomly selected cases [2].
• Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: a multi-institutional retrospective study of 243 patients [26].
• These findings support the validity in design of anchor residue substitution in SYT-SSX fusion gene-derived peptide, and provide a potential clue to the current stagnation in vaccination trials of fusion gene-derived natural junction peptides [27].

References