文章目录

急性淋巴细胞白血病显示出一个独特的高度甲基化的基因组

原文发布日期：2022-05-19

英文摘要：

DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data from large cohorts at a genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing across ALL subtypes, leukemia cell lines and healthy hematopoietic cells, and show that unlike most cancers, ALL samples exhibit CpG island hypermethylation but minimal global loss of methylation. This was most pronounced in T cell ALL and accompanied by an exceptionally broad range of hypermethylation of CpG islands between patients, which is influenced by TET2 and DNMT3B. These findings demonstrate that ALL is characterized by an unusually highly methylated genome and provide further insights into the non-canonical regulation of methylation in cancer. 摘要翻译：

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文章：

急性淋巴细胞白血病显示出一个独特的高度甲基化的基因组

Acute lymphoblastic leukemia displays a distinct highly methylated genome

原文发布日期：2022-05-19

英文摘要：

DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data from large cohorts at a genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing across ALL subtypes, leukemia cell lines and healthy hematopoietic cells, and show that unlike most cancers, ALL samples exhibit CpG island hypermethylation but minimal global loss of methylation. This was most pronounced in T cell ALL and accompanied by an exceptionally broad range of hypermethylation of CpG islands between patients, which is influenced by TET2 and DNMT3B. These findings demonstrate that ALL is characterized by an unusually highly methylated genome and provide further insights into the non-canonical regulation of methylation in cancer. 摘要翻译：

DNA甲基化在发育过程中被紧密调控，并且在健康细胞中稳定保持。与此相反的是，癌细胞通常表现为全球性DNA甲基化的缺失，伴随CpG岛超甲基化现象。在急性淋巴白血病（ALL）这一最常见的儿童癌症中，研究发现CpG甲基化变化与基因型关系及结果相关联，但大规模群体研究数据尚缺乏。本研究通过在整个基因组进行甲基化硫代胸腺嘧啶嘧啶酸解 sequencing（BS-seq），涵盖了ALL亚型、白血病细胞系和健康造血干细胞，并且发现与大多数癌症不同，ALL样本表现出CpG岛超甲基化现象，但全球性甲基化缺失较微弱。这种差异在T细胞白血病中最为明显，伴随着患者之间的CpG岛超甲基化范围异常广泛，在某种程度上受到TET2和DNMT3B的调控。这些发现表明ALL具有高度不寻常的甲基化特征，并为癌症中非典型甲基化的调控机制提供了进一步的见解。