The Impact of DNA Methylation in Hematopoietic Malignancies.
The Impact of DNA Methylation in Hematopoietic Malignancies.
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DOI：
10.1016/j.trecan.2015.12.006
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发表时间：
2016-02-01
期刊：
影响因子：
18.4
通讯作者：
Aifantis I
中科院分区：
文献类型：
--
作者：
Guillamot M;Cimmino L;Aifantis I
异常DNA甲基化是包括血液恶性肿瘤在内的癌症的特征性特征。DNA甲基化调节因子DNMT 3A、TET 1/2和IDH 1/2的突变在白血病和淋巴瘤中复发。AML和淋巴瘤的亚型具有特异性和独特的DNA甲基化模式。调控区域如启动子CpG岛、CpG岸和增强子在转化期间显示甲基化的变化。然而，在许多小鼠模型和人类研究中报道的甲基化和基因表达变化之间的相关性较差，反映了异常DNA甲基化促进恶性肿瘤的精确分子机制的复杂性。本文就造血系统恶性肿瘤中DNA甲基化异常的机制及其在肿瘤预后、异质性和复发中的重要性作一综述。
Aberrant DNA methylation is a characteristic feature of cancer including blood malignancies. Mutations in the DNA methylation regulators DNMT3A, TET1/2 and IDH1/2 are recurrent in leukemia and lymphoma. Specific and distinct DNA methylation patterns characterize subtypes of AML and lymphoma. Regulatory regions such as promoter CpG islands, CpG shores and enhancers show changes in methylation during transformation. However, the reported poor correlation between changes in methylation and gene expression in many mouse models and human studies reflects the complexity in the precise molecular mechanism for why aberrant DNA methylation promotes malignancies. This review will summarize current concepts regarding the mechanisms behind aberrant DNA methylation in hematopoietic malignancy and discuss its importance in cancer prognosis, tumor heterogeneity and relapse.