Issues

Amplification of EGFR is common in cancer cells and often occurs on extrachromosomal DNA Clarke and colleagues discovered previously unknown mechanisms that modulate this EGFR copy-number gain Specifically, methylation of histone 3 at lysine residue 9 or 27 (H3K9Me or H3K27Me) decreased EGFR amplification and expression In contrast, H3K4Me enhanced EGFR amplification Interestingly, exposure to hypoxic conditions or treatment with EGFR's preferred ligand, EGF, both promoted EGFR amplification In both cases, this effect was mediated by the H3K9/36 demethylase KDM4A Further investigation of these newly uncovered pathways may lead to the identification of new drug targets or mechanisms of resistance to EGFR inhibitors For details, please see the article by Clarke and colleagues on page 306.