title: p53 mutation spectra for squamous cell carcinomas at different levels of human bronchial branches.
abstract: The question of whether squamous cell carcinomas (SCCs) arising in different sites of lung are caused by different etiological factors is of obvious importance for prevention, early detection and effective treatment. We here subclassified a large series of resected SCCs (74 cases) into 3 tumor-sites, central (main to segmental bronchi), intermediate (subsegmental to sub-subsegmental) and peripheral (distal to sub-subsegmental bronchi), and examined relationships with p53 mutational spectra and smoking history to provide clues to etiological factors. The rate for G-->A transitions at CpG sites considered to be caused by endogenous mechanism was higher in central (40%) than in intermediate (0%) and peripheral (14%) lesions, in spite of highest percentage of heavy smokers. In contrast, G-->T transversions associated with tobacco smoke carcinogens were most frequent (50%) in the intermediate location, although proportions of heavy smoker's ratio were the same among the locations when confined to p53 mutation cases. In the periphery, other mutations were highest (67%) compared with 33 and 50% in the central and intermediate regions, respectively. Thus, different etiological factors may be playing causal roles in the development of SCCs in different locations of bronchial tree. Furthermore, the results suggest that more extensive study of the influence of tobacco smoke carcinogens on endogenous mechanisms is warranted.
authors.affiliation: Laboratory of Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Kanagawa, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Shimmyo
authors.forename: Takehisa
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Youhei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Ken
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Osada
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001980:Bronchi / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D012907:Smoking / Q000009:adverse effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53