Mounting evidence exists that the activation of proto-oncogene by somatic mutation plays an important roles in the development of human
cancers. Recent reports revealed that the
kinase domain of ERBB2 gene, a proto-oncogene, is somatically mutated in the
lung adenocarcinomas, suggesting the mutated ERBB2 gene may act as an oncogene in human
cancers. The purpose of this was to see whether the ERBB2
kinase domain is mutated in other
lung cancer types besides the
adenocarcinoma. Here, we performed mutational analysis of the ERBB2
kinase domain by polymerase chain reaction-single strand conformation polymorphism assay in 114 non-
adenocarcinoma type non-small cell
lung cancers (NSCLCs) tissue samples, including 100
squamous cell carcinomas, three
adenosquamous carcinomas and 11
large cell carcinomas. We detected the ERBB2
kinase domain mutation in one
squamous cell carcinoma (1.0%). The detected ERBB2 mutation showed G to C transversion at bp 2305 (2305G>C), which would result in the substitution of Asp to His at
codon 769 (D769H). The
amino acid D769 is located in the alpha-helix within the
kinase domain, which is important in the binding of
ATP with ERBB2. We simultaneously analyzed the somatic mutations of EGFR, K-RAS, PIK3CA and BRAF genes in the
squamous cell carcinoma with the ERBB2 mutation, and found that the
tumor did not harbor any EGFR or ERBB2 or K-RAS or PIK3CA or BRAF gene mutation, either. This study demonstrated that in addition to
lung adenocarcinoma ERBB2
kinase domain mutation could occur in lung
squamous cell carcinomas, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations may occasionally contribute to the development of lung
squamous cell carcinomas.