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Updated: Jul 6, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines
Pedro P Medina1, Octavio A Romero, Takashi Kohno
1Lung Cancer Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncologicas(CNIO), Madrid, Spain.
Abstract:
Components of the SWI/SNF chromatin-remodeling complex, such as INI1, are inactivated in human cancer and, thus, act as tumor suppressors. Here we screened for mutations the entire coding sequence of BRG1 (SMARCA4), which encodes the ATPase of the complex, in 59 lung cancer cell lines of the most common histopathological types. Mutations were detected in 24% of the cancer cell lines, many of them in cells commonly used for lung cancer research. All mutations were homozygous and most predicted truncated proteins. The alterations were significantly more frequent in the non-small-cell lung cancer (NSCLC) type (13/37, 35%) as compared to the small-cell lung cancer (SCLC) type (1/19, 5%) (P<0.05; Fisher's Exact test) and BRG1 was the fourth most frequently altered gene in NSCLC cell lines. BRG1 mutations coexisted with mutations/deletions at KRAS, LKB1, NRAS, P16, and P53. However, alterations at BRG1 always occurred in the absence of MYC amplification, suggesting a common role in lung cancer development. In conclusion, our data strongly support that BRG1 is a bona fide tumor suppressor and a major factor in lung tumorigenesis.
Insights
BRG1 (SMARCA4) mutations inactivate this tumor suppressor in lung cancer cells. These alterations are frequent in non-small-cell lung cancer, highlighting BRG1
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- SWI/SNF chromatin-remodeling complex components, like INI1, function as tumor suppressors.
- Inactivation of these components is observed in human cancers.
Purpose of the Study:
- To screen for mutations in the entire coding sequence of BRG1 (SMARCA4), the ATPase subunit of the SWI/SNF complex.
- To investigate the frequency and characteristics of BRG1 mutations in lung cancer cell lines.
Main Methods:
- Screening of the complete coding sequence of BRG1 (SMARCA4) for mutations.
- Analysis of 59 lung cancer cell lines representing common histopathological types.
- Statistical analysis, including Fisher's Exact test, to compare mutation frequencies between non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC).
Main Results:
- Mutations in BRG1 were detected in 24% of lung cancer cell lines.
- Alterations were significantly more frequent in NSCLC (35%) than SCLC (5%).
- BRG1 mutations were homozygous, often predicted truncated proteins, and co-occurred with other cancer-related gene mutations but not MYC amplification.
Conclusions:
- BRG1 (SMARCA4) functions as a bona fide tumor suppressor in lung cancer.
- BRG1 is a significant factor in lung tumorigenesis, particularly in NSCLC.
- BRG1 mutations represent a potential therapeutic target in lung cancer.
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