Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines.
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.
Medina
Pedro P
PP
Lung Cancer Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncologicas(CNIO), Madrid, Spain.
Romero
Octavio A
OA
Kohno
Takashi
T
Montuenga
Luis M
LM
Pio
Ruben
R
Yokota
Jun
J
Sanchez-Cespedes
Montse
M
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000235:genetics*; D017931:DNA Primers; D020868:Gene Silencing; D016259:Genes, myc; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases