Delineating SWI/SNF gene and subtype expression in cancer
Vilma Canfjorden1, Malin Lindén1,2, Tobias Österlund1,2,3
1Department of Laboratory Medicine, Sahlgrenska Center for Cancer Research, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 413 90, Gothenburg, Sweden.
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.
Insights
SWI/SNF gene mutations impact cancer epigenetics. This study reveals distinct SWI/SNF gene expression signatures across 33 tumor types, offering insights for targeted cancer therapies.
Area of Science:
- Cancer Genomics
- Epigenetics
- Chromatin Remodeling
Background:
- Mutations in SWI/SNF chromatin remodeling complex genes occur in ~20% of cancers.
- These mutations can disrupt epigenetic regulation and lead to abnormal gene expression.
- Understanding SWI/SNF gene expression across cancer types and its relation to mutations is crucial.
Purpose of the Study:
- To comprehensively profile SWI/SNF gene and subtype expression across diverse cancer types.
- To investigate the influence of tissue of origin and SWI/SNF mutations on gene expression.
- To identify distinct SWI/SNF expression signatures and their potential clinical implications.
Main Methods:
- Analyzed DNA and mRNA expression data for all 29 SWI/SNF genes from ~11,000 samples across 33 tumor types via The Cancer Genome Atlas.
- Compared SWI/SNF gene expression levels and subtype variations (cBAF, PBAF, GBAF) across tumor types.
- Correlated SWI/SNF gene mutations with downstream gene expression changes.
Main Results:
- Identified significant variations in ACTL6B, DPF1, DPF3, and SMARCD3 expression among tumor types.
- Discovered distinct SWI/SNF gene expression signatures in 10 out of 33 tumor types, partly influenced by tissue of origin.
- Found that SWI/SNF mutations minimally affect gene expression but are linked to altered epigenetic regulation programs in specific cancers.
Conclusions:
- Provides a detailed landscape of SWI/SNF gene and subtype expression across human cancers.
- Highlights the potential of SWI/SNF expression patterns as biomarkers.
- Suggests SWI/SNF pathway alterations as targets for novel cancer therapies.
