title: 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.
authors.affiliation: Advance Research Laboratory, Hitachi Ltd., Hatoyama-machi, Hiki-gun, Saitama 350-0395, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Kiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Tomizawa
authors.forename: T
authors.initials: T
authors.lastname: Kohno
authors.forename: J
authors.initials: J
authors.lastname: Yokota
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000235:genetics* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D018388:Codon, Terminator; D005091:Exons; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking; D014407:Tumor Cells, Cultured
chemical_list: D018388:Codon, Terminator