Jinxiu Li, Timothy S Mulvihill, Li Li, Jared J Barrott, Mary L Nelson, Lena Wagner, Ian C Lock, Amir Pozner, Sydney Lynn Lambert, Benjamin B Ozenberger, Michael B Ward, Allie H Grossmann, Ting Liu, Ana Banito, Bradley R Cairns, Kevin B Jones
Reduced protein levels of SMARCB1 (also known as BAF47, INI1, SNF5) have long been observed in synovial sarcoma. Here, we show that combined Smarcb1 genetic loss with SS18-SSX expression in mice synergized to produce aggressive tumors with histomorphology, transcriptomes, and genome-wide BAF-family complex distributions distinct from SS18-SSX alone, indicating a defining role for SMARCB1 in synovial sarcoma. Smarcb1 silencing alone in mesenchyme modeled epithelioid sarcomagenesis. In mouse and human synovial sarcoma cells, SMARCB1 was identified within PBAF and canonical BAF (CBAF) complexes, coincorporated with SS18-SSX in the latter...
October 2021: Cancer Discovery