Epigenetic priming promotes acquisition of tyrosine kinase inhibitor resistance and oncogene amplification in human lung cancer.

ABSTRACT: In mammalian cells, gene copy number is tightly controlled to maintain gene expression and genome stability. However, a common molecular feature across cancer types is oncogene amplification, which promotes cancer progression by drastically increasing the copy number and expression of tumor-promoting genes. For example, in tyrosine kinase inhibitor (TKI)-resistant lung adenocarcinoma (LUAD), oncogene amplification occurs in over 40% of patients' tumors. Despite the prevalence of oncogene amplification in TKI-resistant tumors, the mechanisms facilitating oncogene amplification are not fully understood. Here, we find that LUADs exhibit a unique chromatin signature demarcated by strong CTCF and cohesin deposition in drug-naïve tumors, which correlates with the boundaries of oncogene amplicons

SUBMITTER: Starble RM 

PROVIDER: S-EPMC11838195 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature