Prevalence and specificity of LKB1 genetic alterations in lung cancers

S. Matsumoto, R. Iwakawa, K. Takahashi, T. Kohno, Y. Nakanishi, Y. Matsuno, K. Suzuki, M. Nakamoto, E. Shimizu, J. D. Minna, J. Yokota

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)5911-5918
Number of pages8
JournalOncogene
Volume26
Issue number40
DOIs
StatePublished - Aug 30 2007

Fingerprint

Lung Neoplasms
Cell Line
Neoplasms
Peutz-Jeghers Syndrome
Large Cell Carcinoma
Mutation
Germ-Line Mutation
Tumor Cell Line
Point Mutation
Non-Small Cell Lung Carcinoma
Smoking
Lung
Adenocarcinoma of lung

Keywords

  • Deletion
  • LKB1
  • Lung cancer mutation
  • Poor differentiation
  • Smoking

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Matsumoto, S., Iwakawa, R., Takahashi, K., Kohno, T., Nakanishi, Y., Matsuno, Y., ... Yokota, J. (2007). Prevalence and specificity of LKB1 genetic alterations in lung cancers. Oncogene, 26(40), 5911-5918. https://doi.org/10.1038/sj.onc.1210418

Prevalence and specificity of LKB1 genetic alterations in lung cancers. / Matsumoto, S.; Iwakawa, R.; Takahashi, K.; Kohno, T.; Nakanishi, Y.; Matsuno, Y.; Suzuki, K.; Nakamoto, M.; Shimizu, E.; Minna, J. D.; Yokota, J.

In: Oncogene, Vol. 26, No. 40, 30.08.2007, p. 5911-5918.

Research output: Contribution to journalArticle

Matsumoto, S, Iwakawa, R, Takahashi, K, Kohno, T, Nakanishi, Y, Matsuno, Y, Suzuki, K, Nakamoto, M, Shimizu, E, Minna, JD & Yokota, J 2007, 'Prevalence and specificity of LKB1 genetic alterations in lung cancers', Oncogene, vol. 26, no. 40, pp. 5911-5918. https://doi.org/10.1038/sj.onc.1210418
Matsumoto S, Iwakawa R, Takahashi K, Kohno T, Nakanishi Y, Matsuno Y et al. Prevalence and specificity of LKB1 genetic alterations in lung cancers. Oncogene. 2007 Aug 30;26(40):5911-5918. https://doi.org/10.1038/sj.onc.1210418
Matsumoto, S. ; Iwakawa, R. ; Takahashi, K. ; Kohno, T. ; Nakanishi, Y. ; Matsuno, Y. ; Suzuki, K. ; Nakamoto, M. ; Shimizu, E. ; Minna, J. D. ; Yokota, J. / Prevalence and specificity of LKB1 genetic alterations in lung cancers. In: Oncogene. 2007 ; Vol. 26, No. 40. pp. 5911-5918.
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