Residual Complexes Containing SMARCA2 (BRM) Underlie the Oncogenic Drive of SMARCA4 (BRG1) Mutation

• DOI: 10.1128/mcb.01372-13
• Publication Date: 2014-01-14T05:01:34Z
• Authors: Boris G. Wilson; Katherine C. Helming; Xiaofeng Wang; Youngha Kim; Francisca Vazquez; Zainab Jagani; William C. Hahn; Charles W. M. Rob...
• Keywords: SMARCA4; SWI/SNF

Collectively, genes encoding subunits of the SWI/SNF (BAF) chromatin remodeling complex are mutated in 20% all human cancers, with SMARCA4 (BRG1) subunit being one most frequently mutated. The modulates through activity two mutually exclusive catalytic subunits, and SMARCA2 (BRM). Here, we show that a SMARCA2-containing residual underlies oncogenic mutant cancers. We demonstrate exists cell lines plays essential roles cellular proliferation. Further, using data from loss-of-function screening 165 cancer lines, identify as an gene lines. Mechanistically, reveal Smarca4 inactivation leads to greater incorporation nonessential into complex. these results role for oncogenesis caused by loss ATPase bromodomain-containing potential therapeutic target