Epigenetic Events in Lung Cancer: Chromatin Remodeling and DNA Methylation

Abstract Epigenetic alterations, layered onto the genome, determine gene expression patterns and include histone modifications, chromatin remodeling, and DNA methylation, with implications for detection, prognostication, and therapy in lung cancer. Distinct cellular phenotypes are based on differential gene expression. Epigenetic mechanisms include DNA methylation, histone modifications, regulatory RNAs, genome-organizing proteins, and chromatin remodeling complexes. Both genetic and epigenetic alterations can contribute to lung cancer and they can interact. Numerous DNA methylation changes are seen in lung cancer, most commonly hypermethylation of promoter CpG-dense regions and loss of methylation in gene bodies. DNA methylation alterations in a variety of bodily fluids can be used as biomarkers for the presence of lung cancer. Epigenetic alternations are in principle reversible; epigenetic therapies thus offer opportunities for treatment by undoing cancer-driving epigenetic changes or by activating targets for therapy. Epigenetics has given new breath to the fight against lung cancer, including in early detection and treatment.