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The clinical implication of SS18-SSX fusion gene in synovial sarcoma.

ABSTRACT: BACKGROUND: The aim of this study is to evaluate distribution and clinical impact of the SS18-SSX fusion gene in patients with synovial sarcoma in China. METHODS: We collected and analysed the clinical data of 88 patients using univariate and multivariate survival analysis. HEK 293T and NIH 3T3 cell lines were transfected with the SS18-SSX1 or SS18-SSX2 gene to determine the respective involvement of these fusion genes in cell proliferation and invasion. RESULTS: Overall survival was significantly better among SS18-SSX2 cases (P=0.001), FNCLCC grade 2 cases (P<0.001), and UICC stage 1 or 2 (P<0.001) by univariate and multivariate survival analysis. SS18-SSX1-positive cells were more proliferative and invasive than SS18-SSX2-positive cells. CONCLUSION: SS18-SSX fusion type is a significant prognostic factor for patients with synovial sarcoma.

SUBMITTER: Ren T

PROVIDER: S-EPMC3798954 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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The clinical implication of SS18-SSX fusion gene in synovial sarcoma.

Ren T T Lu Q Q Guo W W Lou Z Z Peng X X Jiao G G Sun Y Y

British journal of cancer 20130910 8

<h4>Background</h4>The aim of this study is to evaluate distribution and clinical impact of the SS18-SSX fusion gene in patients with synovial sarcoma in China.<h4>Methods</h4>We collected and analysed the clinical data of 88 patients using univariate and multivariate survival analysis. HEK 293T and NIH 3T3 cell lines were transfected with the SS18-SSX1 or SS18-SSX2 gene to determine the respective involvement of these fusion genes in cell proliferation and invasion.<h4>Results</h4>Overall survi ...[more]

PMID: 24022186

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Proteomic signatures corresponding to the SS18/SSX fusion gene in synovial sarcoma.

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The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma.

Project description:Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands. Via KDM2B, SS18-SSX1 binds and aberrantly activates expression of developmentally regulated genes otherwise targets of polycomb-mediated repression, which is restored upon KDM2B depletion, leading to irreversible mesenchymal differentiation. Thus, SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.

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Novel SS18-NEDD4 gene fusion in a primary renal synovial sarcoma.

Project description:We report a primary renal synovial sarcoma with a novel gene fusion and unusual morphology. The patient was a 35-year-old female who was found to have a 5 cm hypocellular, myxoid spindle cell renal neoplasm that subtly permeated amongst native renal tubules. The tumor cells showed elongated hyperchromatic nuclei with ill-defined pale cytoplasm, lacking significant mitotic activity or necrosis. Based on its deceptively bland morphology, the differential diagnosis included mainly benign entities, such as metanephric stromal tumor, mixed epithelial stromal tumor (MEST), and myxoid peripheral nerve sheath tumors. A definitive diagnosis of synovial sarcoma was made only subsequently to RNA-sequencing, which revealed a novel SS18-NEDD4 gene fusion. These results were further confirmed by fluorescence in situ hybridization using custom design break-apart probes for both genes. This case illustrates the utility of targeted RNA-sequencing in the classification of challenging tumors with deceptive morphology and identification of novel gene fusion variants. Apart from the canonical SS18-SSX fusion, this is only the second alternative gene fusion variant described in synovial sarcoma to date, in addition to two cases harboring the SS18L1-SSX1 fusion.

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