Chromatin state profiling reveals PRC2 inhibition as a therapeutic target in NRAS-mutant melanoma

Mol Cell Oncol. 2021 Oct 27;8(5):1986350. doi: 10.1080/23723556.2021.1986350. eCollection 2021.

Abstract

Recently, we have generated 284 epigenomic maps in melanoma. Using chromatin state profiling we identify an association of NRAS-mutants with bivalent Histone H3 lysine 27 trimethylation (H3K27me3) and broad H3K4me3 domains. Reprogramming of bivalent H3K27me3 occurs on critical invasive-regulators and its resolution using Enhancer of Zeste Homolog 2 (EZH2) inhibition reduces invasive capacity and tumor burden in NRAS-mutant patient samples.

Keywords: Melanoma metastasis; bivalent; broad domains; melanoma therapeutics; polycomb repressive complex 2.