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SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression
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Synovial sarcoma (SS) is considered as high-grade tumors with a poor prognosis. Novel therapies targeted at fusion oncogene, SS18-SSX-derived peptide vaccine, epidermal growth factor receptor, and vascular endothelial growth factor are the future hope in SS.
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Data indicate that the oncogene SS18-SSX1 promotes tumorigenesis by increasing the expression of SHC SH2-domain binding protein 1 (SHCBP1), which normally acts as a tumor promoting factor.
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In patients with Colon cancer, the expression of SSX1 gene was associated with a poor prognosis.
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Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors.
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Data show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary synovial sarcoma.
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a rare variant of the SS18-SSX1 fusion transcript, which could not be identified by routine procedures for genetic diagnosis, was detected. In addition, 8 missense mutations of cancer-related genes were confirmed
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SS18-SSX-induced Wnt/beta-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression.
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The mRNA levels of SSX1 and SSX4 are associated with multiple myeloma clinical stage
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These results suggest that the characteristic speckle localization pattern of SS18-SSX is strongly involved in the tumorigenesis through the SSX moiety of the SS18-SSX fusion protein.
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Knockdown of SS18-SSX1 in synovial sarcoma inhibits viability and induces apoptosis.
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Study shows that the SS18-SSX1 oncogenic fusion usurps SWI/SNF-like BAF complexes, resulting in activation of Sox2, which drives proliferation.
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siRNA targeting of SS18-SSX1 has therapeutic potential for the treatment of synovial sarcoma.
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epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects
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existence of fusion with SYT in synovial sarcoma
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A synovial sarcoma of classic morphology contained a novel t(20;X) SS18L1(strong homology to SS18 on Ch20)/SSX1 fusion transcript in which nucleotide 1216 (exon 10) of SS18L1 was fused in-frame with nucleotide 422 (exon 6) of SSX1.
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RT-PCR detection of SSX1 in paraffin-embedded tissue allowed for molecular diagnosis of synovial sarcoma.
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demonstrate differentially expressed genes for the 2 major gene fusion variants in SS, chromosome 18 synovial sarcoma (SS18)/SSX1 and SS18/SSX2, and thereby suggest that these result in different downstream effects
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SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells.
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In conclusion, SS18-SSX and IGF-1R seem to play important but different roles in maintaining malignant growth of synovial sarcoma cells.
