Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Cold Spring Harb Perspect Biol. 2022 Mar 1;14(3):a040956. doi: 10.1101/cshperspect.a040956.
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.
细胞状态从正常向恶性的转变从根本上是由致癌基因突变与染色质的表观遗传改变共同驱动的。这些染色质的改变可能是环境胁迫或种系和/或体细胞突变的结果，这些突变直接改变染色质机器蛋白的结构、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的谱系路径分化，或者驱动一种过度活跃、高度增殖的状态，对高水平的转录输出产生依赖。我们讨论了这些遗传改变如何劫持染色质机器来实现致癌过程，从而揭示癌症治疗的独特弱点和新靶点。
