nature-genetic201211-8

来自西班牙巴萨罗那大学的José Martin-Subero及其同事报道了139例慢性淋巴细胞白血病(CLL)患者的全基因组亚硫酸氢盐测序数据,同时使用高密度的基因芯片获得了两类CLLs和三类B细胞亚型的甲基化组测序数据。他们在与基因内增强子元件紧密相关的基因体中鉴定到广泛分布的低甲基化。相关的研究论文于10月14日在线发表在《Nature Genetics》期刊上。

-2012年11月《自然-遗传》

中文翻译


【题目】使用表观遗传分析检测慢性淋巴细胞白血病中广泛分布的基因体DNA低甲基化

【译文】借助全基因组亚硫酸氢盐测序法和高密度的基因芯片,我们大规模地获得了139例带有变异的或正常的IGHV基因的慢性淋巴细胞白血病(CLL)患者和一些成熟的B细胞亚群的DNA甲基化组的测序数据。CLL的两类分子亚型具有不同的DNA甲基化组,似乎代表了来自不同的正常B细胞亚群的表观遗传印记。基因体中的DNA低甲基化(主要存在于大多数增强子位点中),是天然的B细胞与记忆B细胞之间和CLL的两类分子亚型与正常B细胞之间的主要差异。尽管DNA甲基化和基因表达具有很小的关联性,但是我们鉴定到基因体CpG双核苷酸它的甲基化与基因表达呈现阳性或阴性关联。我们也确定了一个DNA甲基化标签,它可用于区分CLL的新临床亚型。我们认为基因体中的不同甲基化具有的表观遗传组信息可能对白血病的发生具有功能和临床意义。

英文原稿


[Title]: Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia

[Authors]: Marta Kulis, Simon Heath, Marina Bibikova, Ana C Queirós, Alba Navarro, Guillem Clot, Alejandra Martínez-Trillos, Giancarlo Castellano, Isabelle Brun-Heath, Magda Pinyol, Sergio Barberán-Soler, Panagiotis Papasaikas, Pedro Jares, Sílvia Beà, Daniel Rico, Simone Ecker, Miriam Rubio, Romina Royo, Vincent Ho, Brandy Klotzle, Lluis Hernández, Laura Conde, Mónica López-Guerra, Dolors Colomer, Neus Villamor, Marta Aymerich, María Rozman, Mónica Bayes, Marta Gut, Josep L Gelpí, Modesto Orozco, Jian-Bing Fan, Víctor Quesada, Xose S Puente, David G Pisano, Alfonso Valencia, Armando López-Guillermo, Ivo Gut, Carlos López-Otín, Elías Campo & José I Martín-Subero

[Abstract]: We have extensively characterized the DNA methylomes of 139 patients with chronic lymphocytic leukemia (CLL) with mutated or unmutated IGHV and of several mature B-cell subpopulations through the use of whole-genome bisulfite sequencing and high-density microarrays. The two molecular subtypes of CLL have differing DNA methylomes that seem to represent epigenetic imprints from distinct normal B-cell subpopulations. DNA hypomethylation in the gene body, targeting mostly enhancer sites, was the most frequent difference between naive and memory B cells and between the two molecular subtypes of CLL and normal B cells. Although DNA methylation and gene expression were poorly correlated, we identified gene-body CpG dinucleotides whose methylation was positively or negatively associated with expression. We have also recognized a DNA methylation signature that distinguishes new clinico-biological subtypes of CLL. We propose an epigenomic scenario in which differential methylation in the gene body may have functional and clinical implications in leukemogenesis.

原文地址

http://www.nature.com/ng/journal/v44/n11/full/ng.2443.html

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