Human synovial sarcoma is a soft-tissue tumor in which 100% of tumors have a precise translocation involving the SS18 subunit of BAF complexes (90). The t(X;18) chromosomal translocation is the hallmark, diagnostic feature of the disease which results in the direct fusion of 78 amino acids of the C terminus of SSX to the SS18 C terminus. This well established driver, the SS18-SSX oncogenic fusion, overtakes complexes, outcompeting wild-type SS18 (from the one remaining normal allele) and causing the displacement of BAF47, likely an adjacent or nearby subunit in the complex (Fig. 4). The SS18-SSX containing complexes are then retargeted to oncogenic loci such as SOX2 and PAX6, activating these genes by displacement of PRC2 complexes and their H3K27me3 repressive marks. Both the biochemical changes to subunit composition in the complex and the targeting on chromatin can be reversed by removing the SS18-SSX fusion [that is, via short hairpin RNA (shRNA) or CRISPR] or altering the stoichiometric balance of SS18-SSX relative to wild-type SS18 (that is, via wild-type SS18 overexpression) assembling into complexes. It should be noted that this mechanism
