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Genetic alteration of the β-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion

Oncogene volume 20, pages 4249–4257 (2001)Cite this article

Abstract

The β-catenin gene (CTNNB1) has been shown to be genetically mutated in various human malignancies. To determine whether the β-catenin gene is responsible for oncogenesis in thoracic malignancies, we searched for the mutation in 166 lung cancers (90 primary tumors and 76 cell lines), one blastoma and 10 malignant mesotheliomas (two primary tumors and eight cell lines). Among the lung cancers, including 43 small cell lung cancers (SCLCs) and 123 non-small cell lung cancers (NSCLCs), we identified four alterations in exon 3, which is the target region of mutation for stabilizing β-catenin. One primary adenocarcinoma had a somatic mutation from C to G, leading to an amino acid substitution from Ser to Cys at codon 37. Among the cell lines, SCLC NCI-H1092 had a mutation from A to G, leading to an Asp to Gly substitution at codon 6, NSCLC HCC15 had a mutation from C to T, leading to a Ser to Phe substitution at codon 45, and NSCLC NCI-H358 had a mutation from A to G, leading to a Thr to Ala substitution at codon 75. One blastoma also had a somatic mutation from C to G, leading to a Ser to Cys substitution at codon 37. Among the 10 malignant mesotheliomas, we identified a homozygous deletion in the NCI-H28 cell line. Cloning of the rearranged fragment from NCI-H28 indicated that all the exons except exon 1 of the β-catenin gene are deleted and that the deletion junction is 13 kb downstream from exon 1. Furthermore, Northern blot analysis of 26 lung cancer and eight mesothelioma cell line RNAs detected ubiquitous expression of the β-catenin messages except NCI-H28, although Western blot analysis showed that relatively less amounts of protein products were expressed in some of lung cancer cell lines. Our findings suggest that the β-catenin gene is infrequently mutated in lung cancer and that the NCI-H28 homozygous deletion of the β-catenin gene might indicate the possibility of a new tumor suppressor gene residing in this region at 3p21.3, where various types of human cancers show frequent allelic loss.

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Acknowledgements

We would like to acknowledge Dr Kwun M Fong for helpful comments on the manuscript and Ms Hiroko Kako and Ms Yumie Narita for technical support. This work was supported in part by a Grant-in-Aid from Japan Society for Promotion of Science, by a grant from Aichi Cancer Research Foundation to Y Sekido, by NCI grants CA71618 and Lung Cancer SPORE P50 CA70907, and the G Harold and Leila Y Mathers Charitable Foundation to JD Minna.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Nagoya University School of Medicine, Nagoya, 466-8550, Japan

    Kikuo Shigemitsu, Noriyasu Usami, Shoichi Mori, Hiromu Yoshioka, Munehisa Imaizumi & Yuichi Ueda

  2. Department of Clinical Preventive Medicine, Nagoya University School of Medicine, Nagoya , 466-8550, Japan

    Yoshitaka Sekido, Mitsuo Sato & Kaoru Shimokata

  3. First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, 466-8550, Japan

    Yoshitsugu Horio & Yoshinori Hasegawa

  4. Department of Pathology II, Nagoya University School of Medicine, Nagoya, 466-8550, Japan

    Masahide Takahashi

  5. Hamon Center for Therapeutic Oncology Research, Dallas, 75235, Texas, TX, USA

    Scott A Bader, Adi F Gazdar & John D Minna

  6. Department of Internal Medicine, Aichi Cancer Center, Chikusa-ku, Nagoya, 464-8681, Japan

    Toyoaki Hida

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  1. Kikuo Shigemitsu
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Correspondence to Yoshitaka Sekido.

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Shigemitsu, K., Sekido, Y., Usami, N. et al. Genetic alteration of the β-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion. Oncogene 20, 4249–4257 (2001). https://doi.org/10.1038/sj.onc.1204557

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