Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelium with near-normal cells.
Tobacco smoking causes lung cancer(1-3), a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA(4,5). The profound effects of tobacco on the genome of lung cancer cells are well-documented(6-10), but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell
