AbstractThe gene encoding the ATPase of the chromatin remodeling SWI/SNF complexesSMARCA4(BRG1) is often mutated or silenced in tumors, suggesting a role as tumor suppressor. Nonetheless, recent reports show requirement of SMARCA4 for tumor cells growth. Here, we performed a computational meta-analysis using gene expression, prognosis, and clinicopathological data to clarify the role of SMARCA4 and the alternative SWI/SNF ATPase SMARCA2 (BRM) in cancer. We show that while theSMARCA4gene is mostly overexpressed in tumors,SMARCA2is almost invariably downexpressed in tumors. HighSMARCA4expression was associated with poor prognosis in many types of tumors, including liver hepatocellular carcinoma (LIHC), and kidney renal clear cell carcinoma (KIRC). In contrast, highSMARCA2expression was associated with good prognosis. We compared tumors with high versus low expression ofSMARCA4orSMARCA2in LIHC and KIRC cohorts from The Cancer Genome Atlas. While a high expression ofSMARCA4is associated with aggressive tumors, a high expression ofSMARCA2is associated with benign differentiated tumors, suggesting that SMARCA4 and SMARCA2 play opposite roles in cancer. Our results demonstrate that expression ofSMARCA4andSMARCA2have a high prognostic value and challenge the broadly accepted general role of SMARCA4 as a tumor suppressor.