RRC ID 42927
著者 Matsumoto S, Iwakawa R, Takahashi K, Kohno T, Nakanishi Y, Matsuno Y, Suzuki K, Nakamoto M, Shimizu E, Minna JD, Yokota J.
タイトル Prevalence and specificity of LKB1 genetic alterations in lung cancers.
ジャーナル Oncogene
Abstract Germline LKB1 mutations cause Peutz-Jeghers syndrome, a hereditary disorder that predisposes to gastrointestinal hamartomatous polyposis and several types of malignant tumors. Somatic LKB1 alterations are rare in sporadic cancers, however, a few reports showed the presence of somatic alterations in a considerable fraction of lung cancers. To determine the prevalence and the specificity of LKB1 alterations in lung cancers, we examined a large number of lung cancer cell lines and lung adenocarcinoma (AdC) specimens for the alterations. LKB1 genetic alterations were frequently detected in the cell lines (21/70, 30%), especially in non-small cell lung cancers (NSCLCs) (20/51, 39%), and were significantly more frequent in cell lines with KRAS mutations. Point mutations were detected only in AdCs and large cell carcinomas, whereas homozygous deletions were detected in all histological types of lung cancer. Among lung AdC specimens, LKB1 mutations were found in seven (8%) of 91 male smokers but in none of 64 females and/or nonsmokers, and were significantly more frequent in poorly differentiated tumors. The difference in the frequency of LKB1 alterations between cell lines and tumor specimens was likely to be owing to masking of deletions by the contamination of noncancerous cells in the tumor specimens. These results indicate that somatic LKB1 genetic alterations preferentially occur in a subset of poorly differentiated lung AdCs that appear to correlate with smoking males.
巻・号 26(40)
ページ 5911-8
公開日 2007-8-30
DOI 10.1038/sj.onc.1210418
PII 1210418
PMID 17384680
PMC PMC3457639
MeSH AMP-Activated Protein Kinase Kinases Aged Base Sequence Carcinoma / genetics* Cell Line, Tumor Female Gene Expression Regulation, Neoplastic* Humans Lung Neoplasms / genetics* Lung Neoplasms / metabolism* Male Middle Aged Molecular Sequence Data Mutation* Prevalence Protein Serine-Threonine Kinases / genetics* Smoking
IF 7.971
引用数 175
WOS 分野 ONCOLOGY GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞