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Prevalence and specificity of LKB1 genetic alterations in lung cancers

Oncogene volume 26, pages 5911–5918 (2007)Cite this article

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.

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Acknowledgements

This work was supported by Grants-in-Aid from the Ministry of Health, Labor and Welfare of Japan for the 3rd-term Comprehensive 10-year Strategy for Cancer Control and for Cancer Research (16-1), from the program for promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NiBio), and from National Cancer Institute Lung Cancer SPORE (Grant Number: P50CA70907).

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Authors and Affiliations

  1. Biology Division, National Cancer Center Research Institute, Tokyo, Japan

    S Matsumoto, R Iwakawa, K Takahashi, T Kohno, M Nakamoto & J Yokota

  2. Pathology Division, National Cancer Center Research Institute, Tokyo, Japan

    Y Nakanishi

  3. Diagnostic Pathology Division, National Cancer Center Hospital, Tokyo, Japan

    Y Matsuno

  4. Thoracic Surgery Division, National Cancer Center Hospital, Tokyo, Japan

    K Suzuki

  5. Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Tottori, Japan

    S Matsumoto, M Nakamoto & E Shimizu

  6. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Cencter, Dallas, TX, USA

    J D Minna

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  1. S Matsumoto
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  2. R Iwakawa
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  3. K Takahashi
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Correspondence to J Yokota.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Matsumoto, S., Iwakawa, R., Takahashi, K. et al. Prevalence and specificity of LKB1 genetic alterations in lung cancers. Oncogene 26, 5911–5918 (2007). https://doi.org/10.1038/sj.onc.1210418

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  • DOI: https://doi.org/10.1038/sj.onc.1210418

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