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Somatic gain-of-function mutations that drive cancer pathogenesis are well established opportunities for therapeutic intervention, as demonstrated by the clinical efficacy of kinase inhibitors in kinase-mutant malignancies. Here, we discuss the recently discovered gain-of-function mutations in chromatin-regulatory machineries that promote the pathogenesis of cancer. The current understanding of the underlying molecular mechanisms and the therapeutic potential for direct chemical inhibition will be reviewed.

Gain-of-function mutation of chromatin regulators as a tumorigenic mechanism and an opportunity for therapeutic intervention