DNA甲基化在血液系统恶性肿瘤中的影响
The Impact of DNA Methylation in Hematopoietic Malignancies.
作者信息
Guillamot Maria, Cimmino Luisa, Aifantis Iannis
机构信息
Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, NY, 10016, USA; Laura and Isaac Perlmutter Cancer Center and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY, 10016, USA.
出版信息
Trends Cancer. 2016 Feb 1;2(2):70-83. doi: 10.1016/j.trecan.2015.12.006.
Abstract
Aberrant DNA methylation is a characteristic feature of cancer including blood malignancies. Mutations in the DNA methylation regulators , and 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.
摘要
异常的DNA甲基化是包括血液恶性肿瘤在内的癌症的一个特征性标志。DNA甲基化调节因子中的突变在白血病和淋巴瘤中经常出现。特定且不同的DNA甲基化模式是急性髓系白血病（AML）和淋巴瘤亚型的特征。启动子CpG岛、CpG岸和增强子等调控区域在细胞转化过程中显示出甲基化变化。然而，许多小鼠模型和人体研究中报道的甲基化变化与基因表达之间的低相关性反映了异常DNA甲基化促进恶性肿瘤的精确分子机制的复杂性。本综述将总结目前关于造血系统恶性肿瘤中异常DNA甲基化背后机制的概念，并讨论其在癌症预后、肿瘤异质性和复发中的重要性。
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