Linked Life Data

15287030

Source:http://linkedlifedata.com/resource/pubmed/id/15287030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-8-2
pubmed:abstractText
The SMARCA4/BRG1 gene product is a component of the SWI-SNF chromatin-remodeling complex and regulates gene expression by disrupting histone-DNA contacts in an ATP-dependent manner. Inactivating mutations of the SMARCA4 gene, on chromosome arm 19p, are present in several human cancer cell lines, including cell lines derived from lung cancers. Interestingly, loss of heterozygosity (LOH) at 19p and absence of the SMARCA4 protein have been reported in lung tumors. To evaluate further the possible contribution of SMARCA4 gene inactivation to lung carcinogenesis, we performed a complete analysis of the SMARCA4 gene to search for (a) point mutations in all 35 coding exons, including an existing splicing variant and the intron-exon boundaries, and (b) abrogation of gene expression through promoter hypermethylation by using the methylation-specific polymerase chain reaction (MSP) assay. We selected genomic DNA from 20 lung primary tumors with LOH on 19p for the screening of point mutations and 10 lung cancer cell lines and 52 lung primary tumors for the MSP analysis. Through our mutational screening, we identified an in-frame and germ-line insertion of 24 bp in exon 4 whose biological relevance is unknown. This variant was not detected in the germ line of the 62 additional individuals analyzed, indicating it is not a common polymorphism. Moreover, two missense alterations were identified in the tumors of 2 patients, a somatic Gly1160Arg mutation and a Ser1176Cys mutation. Neither was present in the germ line of the 51 additional lung cancer individuals tested. Because these mutations lead to substitution of highly conserved amino acids, they may affect the ATPase function of the protein. Finally, no promoter hypermethylation was observed in any lung primary tumor or cancer cell line, indicating that this is not a major mechanism for SMARCA4 inactivation during lung carcinogenesis. In conclusion, our data revealed that somatic point mutations of the SMARCA4 gene are present in a small subset of lung tumors, although mutations affecting the ATPase domain may be a hot-spot for SMARCA4 gene inactivation. We cannot rule out that other mechanisms, such as complete or partial deletions of the SMARCA4 gene, are contributing to the loss of the SMARCA4 protein in lung cancer.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1045-2257
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
170-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15287030-Amino Acid Sequence, pubmed-meshheading:15287030-Base Sequence, pubmed-meshheading:15287030-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:15287030-DNA, Neoplasm, pubmed-meshheading:15287030-DNA Helicases, pubmed-meshheading:15287030-DNA Methylation, pubmed-meshheading:15287030-DNA Primers, pubmed-meshheading:15287030-DNA Transposable Elements, pubmed-meshheading:15287030-Exons, pubmed-meshheading:15287030-Gene Frequency, pubmed-meshheading:15287030-Genetic Testing, pubmed-meshheading:15287030-Humans, pubmed-meshheading:15287030-Lung Neoplasms, pubmed-meshheading:15287030-Molecular Sequence Data, pubmed-meshheading:15287030-Nuclear Proteins, pubmed-meshheading:15287030-Point Mutation, pubmed-meshheading:15287030-Promoter Regions, Genetic, pubmed-meshheading:15287030-Sequence Alignment, pubmed-meshheading:15287030-Sequence Homology, Amino Acid, pubmed-meshheading:15287030-Transcription Factors
pubmed:year
2004
pubmed:articleTitle
Genetic and epigenetic screening for gene alterations of the chromatin-remodeling factor, SMARCA4/BRG1, in lung tumors.
pubmed:affiliation
Lymphoma and Lung Cancer Group, Molecular Pathology Program. Spanish National Cancer Centre (CNIO), Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't