The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma.

Cancer Cell
Authors
Keywords
Abstract

Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.

Year of Publication
2018
Journal
Cancer Cell
Volume
33
Issue
6
Pages
1128-1141.e7
Date Published
2018 06 11
ISSN
1878-3686
DOI
10.1016/j.ccell.2018.05.002
PubMed ID
29861296
PubMed Central ID
PMC6791822
Links
Grant list
DP2 CA195762 / CA / NCI NIH HHS / United States
R01 CA237241 / CA / NCI NIH HHS / United States
T32 GM095450 / GM / NIGMS NIH HHS / United States