The change in cell state from normal to malignant is driven fundamentally by oncogenic mutations in cooperation with epigenetic alterations of chromatin. These alterations in chromatin can be a consequence of environmental stressors or germline and/or somatic mutations that directly alter the structure of chromatin machinery proteins, their levels, or their regulatory function. These changes can result in an inability of the cell to differentiate along a predefined lineage path, or drive a hyperactive, highly proliferative state with addiction to high levels of transcriptional output. We discuss how these genetic alterations hijack the chromatin machinery for the oncogenic process to reveal unique vulnerabilities and novel targets for cancer therapy.

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导致癌症的染色质机制

细胞状态从正常到恶性的变化基本上是由致癌突变与染色质的表观遗传改变共同驱动的。染色质的这些改变可能是环境压力或生殖系和/或体细胞突变的结果，这些突变直接改变染色质机械蛋白的结构、它们的水平或它们的调节功能。这些变化可能导致细胞无法沿着预定义的谱系路径分化，或驱动过度活跃、高度增殖的状态并依赖高水平的转录输出。我们讨论了这些基因改变如何劫持致癌过程的染色质机制，以揭示癌症治疗的独特脆弱性和新靶点。