Age-related DNA methylation in paired normal and tumour breast tissue in Chinese breast cancer patients.
Age-related DNA methylation in paired normal and tumour breast tissue in Chinese breast cancer patients.
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中国乳腺癌患者配对正常和肿瘤乳腺组织中年龄相关的DNA甲基化。
DOI：
10.1080/15592294.2020.1819661
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发表时间：
2021-06
期刊：
影响因子：
3.7
通讯作者：
Yang XR
中科院分区：
文献类型：
--
作者：
Kiely M;Tse LA;Koka H;Wang D;Lee P;Wang F;Wu C;Tsang KH;Chan WC;Law SH;Zhang H;Karlins E;Zhu B;Hutchinson A;Hicks B;Zhu B;Yang XR
年龄相关的DNA甲基化是促进乳腺癌发展的潜在机制。主要针对高加索女性的研究发现，在未患病的乳腺组织中，许多CpG位点的年龄相关甲基化可能会随着时间的推移推动癌症的发展。关于亚洲女性乳腺癌发病年龄通常比白种人年轻的研究很少。我们在已发表的研究中确定了181个与非病变乳腺组织最一致的年龄相关甲基化事件。在先前确定的年龄相关甲基化位点，在亚洲人群的邻近正常和乳腺肿瘤组织中测量了年龄相关甲基化事件。在邻近正常乳腺组织的118个探针中发现了与年龄相关的甲基化。99%的甲基化位点随着年龄的增长而增加，并且主要位于启动子区域的CpG岛上。为了确定与乳腺癌的生物学相关性，我们将重点放在肿瘤中甲基化程度总体高于邻近正常样本的37个位点上。一些与年龄正相关的位点，包括AQP5和CORO6，与基因表达呈负相关。其他几个已知参与抑制癌变的基因包括GPC5和SST，这表明由于衰老导致这些位点表观遗传调控的扰动可能有助于癌变的进展。这项研究强调了非肿瘤组织中与年龄相关的甲基化景观，不仅在研究中是一致的，而且在不同的人群中也是一致的。我们提出了候选年龄相关的甲基化位点作为乳腺癌潜在的表观遗传驱动因素，值得进一步研究。它们可能作为预防年龄相关性乳腺癌的位点特异性去甲基化干预策略的潜在靶点。
Age-related DNA methylation is a potential mechanism contributing to breast cancer development. Studies of primarily Caucasian women have identified many CpG sites of age-related methylation in non-diseased breast tissue possibly driving cancer development over time. There is a paucity of studies involving Asian women whose ages at breast cancer onset are usually younger than Caucasians. We identified the 181 most consistent age-related methylation events in non-diseased breast tissue across published studies. Age-related methylation events were measured in adjacent normal and breast tumour tissue in an exclusively Asian population at the previously identified age-related methylation sites. Age-related methylation was found in 118 probes in adjacent normal breast tissue. Methylation of 99% of these sites was increased with age and predominantly located on CpG islands in promoter regions. To ascertain biological relevance to breast cancer, we focused on the 37 sites with overall higher methylation in tumour compared to adjacent normal samples. Some sites positively related to age, including AQP5 and CORO6, inversely correlated with gene expression. Several others have known involvement in suppression of carcinogenesis including GPC5 and SST, suggesting that perturbation of epigenetic regulation at these sites due to ageing may contribute to the progression of carcinogenesis. This study highlights an age-related methylation landscape in non-tumour tissue, consistent not just across studies, but also across different populations. We present candidate age-related methylation sites warranting further investigation as potential epigenetic drivers of breast cancer. They may serve as potential targets of site-specific demethylation intervention strategies for the prevention of age-related breast cancer.
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全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
5.7
作者：
Hofstatter, Erin W.;Horvath, Steve;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
DOI：
10.1186/s13058-017-0821-x
发表时间：
2017-03-17
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Li M;Tse LA;Chan WC;Kwok CH;Leung SL;Wu C;Yu WC;Lee PM;Tsang KH;Law SH;Vermeulen R;Gu F;Caporaso NE;Yu IT;Wang F;Yang XR
通讯作者：
Yang XR
影响因子：
5.7
作者：
Legendre C;Gooden GC;Johnson K;Martinez RA;Liang WS;Salhia B
通讯作者：
Salhia B
DOI：
10.18632/aging.101414
发表时间：
2018-04-18
期刊：
Aging
影响因子：
--
作者：
Levine ME;Lu AT;Quach A;Chen BH;Assimes TL;Bandinelli S;Hou L;Baccarelli AA;Stewart JD;Li Y;Whitsel EA;Wilson JG;Reiner AP;Aviv A;Lohman K;Liu Y;Ferrucci L;Horvath S
通讯作者：
Horvath S