DNA 甲基化模式可将衰老与转化潜能区分开来，并提示癌症风险。
DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk.
机构信息
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Cancer Cell. 2018 Feb 12;33(2):309-321.e5. doi: 10.1016/j.ccell.2018.01.008.
Overall shared DNA methylation patterns between senescence (Sen) and cancers have led to the model that tumor-promoting epigenetic patterns arise through senescence. We show that transformation-associated methylation changes arise stochastically and independently of programmatic changes during senescence. Promoter hypermethylation events in transformation involve primarily pro-survival and developmental genes, similarly modified in primary tumors. Senescence-associated hypermethylation mainly involves metabolic regulators and appears early in proliferating "near-senescent" cells, which can be immortalized but are refractory to transformation. Importantly, a subset of transformation-associated hypermethylated developmental genes exhibits highest methylation gains at all age-associated cancer risk states across tissue types. These epigenetic changes favoring cell self-renewal and survival, arising during tissue aging, are fundamentally important for stratifying cancer risk and concepts for cancer prevention.
衰老（Sen）和癌症之间整体共享的 DNA 甲基化模式导致了这样的模型，即促进肿瘤的表观遗传模式是通过衰老产生的。我们表明，转化相关的甲基化变化是随机出现的，与衰老过程中的程序性变化无关。转化中启动子超甲基化事件主要涉及生存和发育基因，这些基因在原发性肿瘤中也被类似地修饰。衰老相关的高甲基化主要涉及代谢调节剂，并且在增殖的“近衰老”细胞中很早就出现，这些细胞可以永生化，但对转化有抗性。重要的是，在所有与年龄相关的癌症风险状态下，与转化相关的超甲基化发育基因的亚组表现出最高的甲基化增益，跨越组织类型。这些有利于细胞自我更新和生存的表观遗传变化，在组织衰老过程中产生，对于癌症风险分层和癌症预防概念至关重要。
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