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.

中文翻译：

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DNA甲基化模式将衰老与转化潜能分开，并表明患癌症的风险。

衰老（Sen）和癌症之间总体共有的DNA甲基化模式导致了该模型，即促进肿瘤的表观遗传模式是通过衰老产生的。我们表明，与转化相关的甲基化变化是随机发生的，并且与衰老过程中的程序变化无关。转化中的启动子高甲基化事件主要涉及生存基因和发育基因，在原发性肿瘤中也有类似的修饰。衰老相关的高甲基化主要涉及代谢调节剂，并出现在增殖的“近衰老”细胞的早期，该细胞可以被永生化，但难以转化。重要的是，在整个组织类型中，与年龄相关的所有癌症风险状态下，与转化相关的高甲基化发育基因的子集均表现出最高的甲基化增益。