Fusions of the SYT and SSX genes in synovial sarcoma

Abstract

Synovial sarcomas are high grade spindle cell tumors that are divided into two major histologic subtypes, biphasic and monophasic, according to the respective presence or absence of a well-developed glandular epithelial component. They contain in essentially all cases a t(X;18) representing the fusion of SYT (at 18q11) with either SSX1 or SSX2 (both at Xp11). Neither SYT, nor the SSX proteins contain DNA-binding domains. Instead, they appear to be transcriptional regulators whose actions are mediated primarily through protein-protein interactions, with BRM in the case of SYT, and with Polycomb group repressors in the case of SSX. Ongoing work on the SYT-SSX fusion and synovial sarcoma should yield a variety of data of broader biological interest, in areas such as BRM and Polycomb group function and dysfunction, transcriptional targets of SYT-SSX proteins and their native counterparts, differential gene regulation by SYT-SSX1 and SYT-SSX2, control of glandular morphogenesis, among others.