Prognostic Implications of SMARCA4, ARID1A, and Other BAF Mutations in Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) outcomes have improved remarkably with the widespread use of immune checkpoint inhibitors and small molecule inhibitors targeting driver mutations. Nevertheless, many patients continue to experience suboptimal outcomes. The prevalence of mutations in the BAF (BRG1/BRM-associated factor) chromatin remodeling complexes may represent an opportunity to help close this gap: These critical regulators of chromatin accessibility are mutated in approximately a quarter of NSCLC cases, and numerous retrospective reports have evaluated the impact of these mutations on clinical outcomes. Here, we appraise the varying and occasionally divergent evidence for BAF complex mutations as predictive and prognostic biomarkers in NSCLC.

We conclude that these mutations hold promise as refinements to existing prognostic and treatment algorithms, with SMARCA4 mutations imparting poor prognosis, ARID1A mutations predicting better prognosis with immune checkpoint inhibitor therapy, and ARID1A-epithelial growth factor receptor (EGFR) comutations being associated with insensitivity to EGFR tyrosine kinase inhibitor therapy. Additional research should focus on large, prospective studies that will allow better quantification of the impact of BAF complex mutations.

A growing body of evidence indicates that BAF complex mutations have important prognostic implications. These may be leveraged for risk stratification and therapeutic selection in patients with non-small cell lung cancer.