Delineating SWI/SNF gene and subtype expression in cancer

Abstract Background Approximately 20% of all cancers contain mutations in genes coding for components of the SWI/SNF chromatin remodeling complex, which exists in three main subtypes: cBAF, PBAF, and GBAF. Mutations in SWI/SNF genes may disrupt chromatin remodeling and deregulate epigenetic processes, leading to aberrant gene expression profiles. However, the gene expression profiles of SWI/SNF genes and subtypes across different tumor types in relation to SWI/SNF mutations remain poorly understood. Results In this study, we profile the expression levels of all 29 SWI/SNF genes in 33 tumor types using DNA and mRNA data from The Cancer Genome Atlas, comprising approximately 11,000 samples. We find that ACTL6B , DPF1 , DPF3 and SMARCD3 vary the most among tumor types and that 10 out of 33 tumor types show distinct SWI/SNF gene expression signatures. The SWI/SNF gene expression in tumors are partly influenced by their tissue of origin. Furthermore, the mean expression levels of SWI/SNF subtype-specific genes are overall similar between tumor types, with higher variations in cBAF compared to PBAF and GBAF. Mutations in SWI/SNF genes result in only minor changes in SWI/SNF gene expression levels but are associated with downstream regulation of transcriptional programs linked to epigenetic regulation, especially in colon adenocarcinoma, kidney renal clear cell carcinoma, stomach adenocarcinoma and uterine corpus endometrial carcinoma. Conclusions Our study provides insights into SWI/SNF gene and subtype expression in cancer, which may contribute to the development of biomarkers and targeted therapies.