DNA Methyltransferase inhibition reverses epigenetically embedded phenotypes in lung cancer preferentially affecting Polycomb target genes

Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer with Reduced Representation Bisulfite Sequencing. DNMT-inhibition by 5-Azacytidine at low concentrations reverted the pro-metastatic phenotype. 5-Azacytidine led to preferential loss of DNA methylation at sites that were DNA hypermethylated during the in vivo selection. Changes in DNA methylation persisted over time.

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Hascher A, Haase AK, Hebestreit K, Rohde C, Klein HU, Rius M, Jungen D, Witten A, Stoll M, Schulze I, Ogawa S, Wiewrodt R, Tickenbrock L, Berdel WE, Dugas M, Thoennissen NH, Müller-Tidow C