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Histone Lysine Methylation Dynamics Control EGFR DNA Copy-Number Amplification

ABSTRACT: Acquired chromosomal DNA copy gains are a feature of many tumors; however, the mechanisms that underpin oncogene amplifi cation are poorly understood. Recent studies have begun to uncover the importance of epigenetic states and histone lysine methyltrans_x0002_ferases (KMT) and demethylases (KDM) in regulating transient site-specifi c DNA copy-number gains (TSSG). In this study, we reveal a critical interplay between a myriad of lysine methyltransferases and demethylases in modulating H3K4/9/27 methylation balance to control extrachromosomal amplifi ca_x0002_tion of the EGFR oncogene. This study further establishes that cellular signals (hypoxia and EGF) are able to directly promote EGFR amplifi cation through modulation of the enzymes controlling EGFR copy gains. Moreover, we demonstrate that chemical inhibitors targeting specifi c KMTs and KDMs are able to promote or block extrachromosomal EGFR amplifi cation, which identifi es potential therapeu

ORGANISM(S): Homo sapiens

PROVIDER: GSE315481 | GEO | 2026/01/07

REPOSITORIES: GEO

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