SS18::SSX redistributes BAF chromatin remodelers selectively to activate and repress transcription [RNA-Seq]

Synovial sarcoma (SS) is a rare malignancy, involves a t(X;18) chromosomal translocation that creates a fusion gene SS18-SSX. SS18 is a chromatin remodeling BAF-complexes component, which incorporated in CBAF and GBAF (non-canonical ncBAF). Our previous studies determined that incorporation of the fusion oncoprotein caused degradation of CBAF complexes, emphasizing a critical oncogenic function of GBAF and PBAF in synovial sarcomagenesis. To determine the SyS dependencies on different subtypes of BAF complexes during tumor development in vivo, we used our SyS mouse model combined with genetic disruption of specific BAF complexes components ARID1A/B or PBRM1. In this study, our fundings suggest that depletion of ARID1A and ARID1B sped tumorigenesis, without significant change in the histomorphology of the developing tumors. Loss of PBRM1 also led to faster tumor growing, but Pbrm1-silenced tumors lacked the full array of SyS histomorphologies observed in wildtype tumors. Overall, Arid1a or Arid1b disruption rendered tumor transcriptomes that clustered within the hSS2 tumor transcriptomes, unlike Pbrm1 disrupted tumors.