Importantly, the expression of SS18-SSX is necessary and sufficient for the development of synovial sarcoma, as demonstrated in transgenic mice wherein the conditional expression of SS18-SSX in early myoblasts leads to tumor development without the requirement of any cooperative transgenic changes. The resulting SS18-SSX fusion oncogene can be detected in nearly all synovial sarcomas and is used clinically to confirm the diagnosis. The chromosomal translocation t(X 18)(p11.2 q11.2) is the main cytogenetic event in synovial sarcoma and results in the fusion of the BAF complex member SS18 with one of three highly homologous transcriptional repressor genes, SSX1, SSX2 or SSX4. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known.
SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors.
Here we report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. Proximity ligation assay is a recently-developed method that assesses protein-protein interactions in situ.
#Stopping chemdoodle from auto adding hydrogens driver#
Drugs specifically targeting the product of its driver translocation are currently unavailable, in part because the SS18-SSX oncoprotein functions via aberrant interactions within multiprotein complexes. Received: SeptemAccepted: ApPublished: April 21, 2016Ĭonventional cytotoxic therapies for synovial sarcoma provide limited benefit. Nielsen, email: synovial sarcoma, proximity ligation assay, drug screening, HDAC inhibitors, protein-protein association Brodin 3ġDepartment of Pathology and Laboratory Medicine, Vancouver Coastal Health Research Institute and Faculty of Medicine, University of British Columbia, Vancouver, BC, CanadaĢCentre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, BC, CanadaģDepartment of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
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