DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk.
DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk.
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DOI：
10.1016/j.ccell.2018.01.008
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发表时间：
2018-02-12
期刊：
影响因子：
50.3
通讯作者：
Easwaran H
中科院分区：
文献类型：
--
作者：
Xie W;Kagiampakis I;Pan L;Zhang YW;Murphy L;Tao Y;Kong X;Kang B;Xia L;Carvalho FLF;Sen S;Chiu Yen RW;Zahnow CA;Ahuja N;Baylin SB;Easwaran H
衰老（Sen）和癌症之间总体共享的DNA甲基化模式导致了肿瘤促进表观遗传模式通过衰老出现的模型。我们发现，在衰老过程中，转化相关的甲基化变化是随机发生的，并且独立于程序性变化。转化中的启动子超甲基化事件主要涉及促生存和发育基因，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因子，在增殖的“近衰老”细胞中早期出现，这些细胞可以永生化，但难以转化。重要的是，一个转化相关的高甲基化发育基因的子集在所有组织类型的年龄相关癌症风险状态下表现出最高的甲基化增益。这些表观遗传变化有利于细胞自我更新和生存，在组织老化过程中出现，对于癌症风险分层和癌症预防概念至关重要。Xie等人表明，转化相关的甲基化变化是随机发生的，并且独立于衰老而进化。有利于细胞自我更新和存活的转化相关高甲基化基因的子集在衰老和早期肿瘤发生期间表现出最高的甲基化增益。
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 involve metabolic regulators, 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. Xie et al. show that transformation-associated methylation changes arise stochastically and evolve independently of senescence. A subset of transformation-associated hypermethylated genes favoring cell self-renewal and survival exhibits highest methylation gains during aging and early tumorigenesis.
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影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
7
作者：
Easwaran, Hariharan;Johnstone, Sarah E.;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.
影响因子：
9.8
作者：
Bossuyt W;Kazanjian A;De Geest N;Van Kelst S;De Hertogh G;Geboes K;Boivin GP;Luciani J;Fuks F;Chuah M;VandenDriessche T;Marynen P;Cools J;Shroyer NF;Hassan BA
通讯作者：
Hassan BA