In contrast, in human SS tumors, oncogenic, SS18-SSX fusion–bearing complexes appear to have gained the ability to oppose Polycomb complexes (Figs. 4 and 5), at least at genes critical for the proliferative maintenance of these tumors such as SOX2 (36). Although the specific mechanism of this unique gain-of-function phenotype still remains unclear, it is clear that the 78 amino acids confer an advantage to these complexes, which enhances the displacement of Polycomb. This oncogenic eviction of Polycomb can be reversed by stoichiometrically altering the balance of SS18-SSX versus wild-type SS18 within BAF complexes, thereby reversing the complexes to an induced wild-type state, bearing normal subunit composition. Hence, an exciting therapeutic opportunity emerges from these findings, which is distinct from the reverse direction of opposition seen in MRT complexes (36).
