The
beta-catenin gene (CTNNB1) has been shown to be genetically mutated in various human
malignancies. To determine whether the
beta-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
beta-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
beta-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
beta-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
beta-catenin gene is infrequently mutated in
lung cancer and that the NCI-H28 homozygous deletion of the
beta-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.