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Prevalence and specificity of LKB1 genetic alterations in lung cancers

MATSUMOTOL, S ; IWAKAWA, R ; YOKOTA, J ; TAKAHASHI, K ; KOHNO, T ; NAKANISHI, Y ; MATSUNO, Y ; SUZUKI, K ; NAKAMOTO, M ; SHIMIZU, E ; MINNA, J. D

Oncogene, 2007-08, Vol.26 (40), p.5911-5918 [Peer Reviewed Journal]

Basingstoke: Nature Publishing

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Title:
Prevalence and specificity of LKB1 genetic alterations in lung cancers
Author: MATSUMOTOL, S ; IWAKAWA, R ; YOKOTA, J ; TAKAHASHI, K ; KOHNO, T ; NAKANISHI, Y ; MATSUNO, Y ; SUZUKI, K ; NAKAMOTO, M ; SHIMIZU, E ; MINNA, J. D
Subjects: Adenocarcinoma ; Aged ; Base Sequence ; Biological and medical sciences ; Carcinoma ; Carcinoma - genetics ; Cell Line, Tumor ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Contamination ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Neoplastic ; Gene mutations ; Genetic aspects ; Genetic disorders ; Genetics ; Health aspects ; Humans ; LKB1 protein ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Male ; Medical sciences ; Men ; Middle Aged ; Molecular and cellular biology ; Molecular Sequence Data ; Mutation ; Physiological aspects ; Pneumology ; Polyposis ; Prevalence ; Protein-Serine-Threonine Kinases - genetics ; Risk factors ; Smoking ; Tobacco, tobacco smoking ; Toxicology ; Tumor cell lines ; Tumors ; Tumors of the respiratory system and mediastinum
Is Part Of: Oncogene, 2007-08, Vol.26 (40), p.5911-5918
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Description: 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.
Publisher: Basingstoke: Nature Publishing
Language: English

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Prevalence and specificity of LKB1 genetic alterations in lung cancers

MATSUMOTOL, S ; IWAKAWA, R ; YOKOTA, J ; TAKAHASHI, K ; KOHNO, T ; NAKANISHI, Y ; MATSUNO, Y ; SUZUKI, K ; NAKAMOTO, M ; SHIMIZU, E ; MINNA, J. D

Basingstoke: Nature Publishing

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