Comprehensive analysis of p53 gene mutation characteristics in lung carcinoma with special reference to histological subtypes.

Abstract

To date, the characteristics of p53 gene mutations in lung cancer have been extensively investigated. However, current estimates of p53 alterations are inaccurate, since most investigators have limited their analyses to exons 5 to 8 of the p53 gene. We examined 52 lung carcinoma cell lines and 106 primary non-small cell lung carcinomas (NSCLC) for mutations in the entire coding region of the p53 gene, from exons 2 to 11. High resolution single strand conformation polymorphism analysis was performed using a modified electrophoretic apparatus with a high concentration gel (14%) and accurate temperature control. The prevalence of mutations was high (more than 80%) in both small cell lung carcinoma (SCLC) (15 of 18) and NSCLC cell lines (28 of 34), and 9 of 45 mutations (20%) were detected outside the region of exons 5 to 8. The frequency of the mutations in primary NSCLC was 48% (51 of 106) and was significantly different (p=0.01) between adenocarcinoma (39%) and squamous cell carcinoma (67%). A-->G transitions (14%, 6 of 43 cases) as well as G-->T transversions (26%, 11 of 43 cases) were frequently detected with significant strand bias in smoking patients, suggesting that carcinogens causing these mutations are involved in smoking associated lung carcinogenesis.