文章：

CLL疾病进展的遗传和表观遗传分析显示体细胞进化有限，并提示其与记忆细胞发育存在关联

Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development

原文发布日期：2015-04-10

DOI: 10.1038/bcj.2015.14

类型: Original Article

开放获取: 是

英文摘要：

We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells.

摘要翻译： 

我们利用27名患者的系列样本，研究了慢性淋巴细胞白血病（CLL）从惰性进展为侵袭性过程中发生的遗传和表观遗传变化。DNA突变分析将白血病病例分为三类：进化型（26%）、扩增型（26%）和稳定型（47%）。约四分之三的CLL病例几乎不存在遗传亚克隆进化。然而，我们在疾病进展期间发现4752个CpG位点出现显著的复发性DNA甲基化改变，这些位点富集于Polycomb抑制复合体2（PRC2）靶标邻近区域。PRC2靶标附近与疾病进展相关的CpG位点，在白血病进展过程中经历的甲基化改变方向，与正常发育过程中从初始B细胞到记忆B细胞的甲基化变化方向一致。我们的研究表明CLL进展通常不通过亚克隆进化实现，而是特定CpG位点发生复发性甲基化改变。这一结果提示CLL进展可能涉及与正常记忆B细胞生成共通的发育过程。

原文链接：

Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development