Paper - Review

DOI: 10.1038/s41586-020-1961-1

Abstract

Tobacco smoking
→ causes lung cancer
→ a process ← that is driven by more than 60 carcinogens ← in cigarette smoke
← that directly damage & mutate DNA

❗: The profound effects
← of tobacco ← on the the genome of lung cancer cells
→ are well-documented

❓: equivalent data
→ for normal bronchial cells
→ are lacking

Sequenced → whole genomes of 632 colonies
← derived from single bronchial epithelial cells
← across 16 subjects

Tobacco smoking
→ was the major influence ← on mutational burden
∴ Massively increasing ↑ the variance
← both within & between subjects
∴ Generating → several distinct mutational signatures
← 1⃣ of substitutions 2⃣ of insertion & deletions

A population of cells
← in individuals with a history of smoking
→ had mutational burdens ← that were equivalent
→ to those expected ← for people who had never smoked

∴ These cells → had less damage
← from tobacco-specific mutational processes
∴ These cells → were four-fold more frequent
← in ex-smokers ← that current smokers
∴ These cells → had considerable longer telomeres
← that their more-mutated counterparts

1⃣ at 25% of cells → carried driver mutations
2⃣ 6% of cells → had two & three drivers

∴ Tobacco smoking
→ increases → 1⃣ mutational burden 2⃣ cell-to-cell heterogeneity 3⃣ driver mutations
→ promotes → replenishment of (the bronchial epithelium)
← from mitotically quiescents cells ← that have avoided (tobacco mutagenesis)

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