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.

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