Large Clones of Somatic Mutations in the Airway Epithelium of Nonsmokers and Smokers Without Cancer

The human airway epithelium is constantly exposed to the stress of inhaled xenobiotics with the potential to induce somatic mutations Overall design: To test the hypothesis that humans without cancer have sizeable clones of mutated airway epithelium, bronchoscopy and airway brushing was used to sample 10th-12th order small airway epithelium (SAE) of 91 individuals, including nonsmokers (n=33) and smokers (n=58). Using whole exome sequencing with an average depth of 250x to assess the presence of mutations in the SAE compared to blood DNA, we found that almost all individuals sampled had large clones of SAE with identical somatic mutations, smokers had a higher % of probably deleterious variants. Although no driver mutations were found, all variant detected have been previously identified in by lung cancers. Illumina HiSeq 2500 RNA-Seq SAE expression for a subset of the 91 subjects, 17 nonsmokers and 42 smokers, was used to examine the SAE expression of the genes containing deleterious somatic mutations identified in large clones of cells in the small airway epithelium.