Cigarette smoke contributes to epigenetic and genetic changes in lung cancer. But whether and how these alterations interact in lung cancer initiation has remained unclear. Vaz et al. showed that in immortalized lung epithelial cells, exposure to cigarette smoke condensate progressively altered the binding of chromatin-modifying enzymes to DNA and induced changes in DNA methylation in the absence of DNA mutations. Such epigenetically altered cells exhibited a stem cell-like chromatin state that sensitized them to later acquire oncogenic mutations and become lung cancer cells. Modeling cancer initiation is extremely difficult, but this is an important process to understand if we hope to find effective strategies to prevent cancer initiation and/or progression.
