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Targeting SS18-SSX Biology in Synovial Sarcomagenesis

This study investigates the biological consequences of BRD9 degradation in synovial sarcoma, a cancer driven by the SS18::SSX (SSX1 or SSX2) fusion oncoprotein. The study includes human synovial sarcoma cell lines, patient-derived xenograft (PDX) models. Molecular profiling was performed using RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin sequencing (ATAC-seq).

The primary aim was to determine how depletion of the GBAF chromatin remodeling complex subunit BRD9 affects chromatin remodeling activity, transcriptional regulation, and tumor growth in synovial sarcoma. The study found that BRD9 degradation does not disrupt GBAF complex assembly but instead enhances chromatin remodeling activity, maintains or increases chromatin accessibility, and promotes expression of SS18::SSX target genes despite reduced chromatin occupancy. These findings provide a mechanistic explanation for the limited clinical efficacy of BRD9 degraders in synovial sarcoma.

Data available through dbGaP will include raw and processed human genomic and epigenomic datasets generated from patient-derived tumors, including RNA-seq, ChIP-seq, ATAC-seq, together with associated experimental and clinical metadata necessary for data interpretation.