Epigenetic priming promotes tyrosine kinase inhibitor resistance and oncogene amplification.

ABSTRACT: In mammalian cells, gene copy number is controlled to maintain gene expression and genome stability. However, a common molecular feature across cancer types is oncogene amplification, increasing the copy number and expression of tumor-promoting genes and thus promoting cancer progression. For example, in tyrosine kinase inhibitor (TKI)-resistant lung adenocarcinoma (LUAD), oncogene amplification is frequent. Despite the prevalence of oncogene amplification in TKI-resistant tumors, the underlying mechanisms are not fully understood. Here, we find that LUADs exhibit a unique chromatin signature demarcated by strong CTCF and cohesin deposition in drug-naive tumors, which correlates with the boundaries of oncogene amplicons in TKI-resistant LUAD cells. We identify a global chromatin-priming ef

SUBMITTER: Starble RM 

PROVIDER: S-EPMC12819156 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature