Different subtypes of human lung adenocarcinoma caused by different etiological factors: Evidence from p53 mutational spectra

T. Hashimoto, Y. Tokuchi, M. Hayashi, Y. Kobayashi, K. Nishida, S. I. Hayashi, Y. Ishikawa, K. Nakagawa, J. I. Hayashi, E. Tsuchiya

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Human lung adenocarcinomas are only relatively weakly associated with tobacco smoke, and other etiological factors need to be clarified. These may also vary with the histopathology. Because the p53 mutation status (frequency and spectrum) of a carcinoma can provide clues to causative agents, we subclassified 113 adenocarcinomas into five cell types: hobnail, columnar/cuboidal, mixed, polygonal, and goblet (54, 23, 18, 13, and 5, respectively) and investigated relationships with p53 mutations and smoking history. In the hobnail cell type, a low mutational frequency (37%) and a high proportion of transitions (65%), especially G:C to A:T transitions at CpG dinucleotides (45%) associated with spontaneous mutations, were found with a weak relation to tobacco smoke. In contrast, a high mutation frequency (70%) with a higher proportion of transversions (50%), especially G:C to T:A (44%) on the nontranscribed DNA strand, caused by exogenous carcinogenic agents like tobacco smoke, were observed for the columnar cell type, as with squamous cell carcinomas. These results indicate that two major subtypes of lung adenocarcinoma exist, one probably caused by tobacco smoke, and the other possibly due to spontaneous mutations. For the prevention of lung adenocarcinomas, in addition to stopping tobacco smoking, the elucidation of endogenous mechanisms is important.

Original languageEnglish
Pages (from-to)2133-2141
Number of pages9
JournalAmerican Journal of Pathology
Volume157
Issue number6
DOIs
Publication statusPublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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