Chiu Brian C-H, Chen Chang, You Qiancheng, Chiu Rudyard, Venkataraman Girish, Zeng Chang, Zhang Zhou, Cui Xiaolong, Smith Sonali M, He Chuan, Zhang Wei
Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
NPJ Genom Med. 2021 Feb 11;6(1):11. doi: 10.1038/s41525-021-00179-8.
The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.
5-甲基胞嘧啶（5mC）与弥漫性大B细胞淋巴瘤（DLBCL）和滤泡性淋巴瘤（FL）的发病机制有关。然而，由5mC通过活性去甲基化产生的5-羟甲基胞嘧啶（5hmC）在淋巴瘤发生中的作用尚不清楚。我们对73例新诊断的DLBCL和FL患者循环游离DNA（cfDNA）中的全基因组5hmC进行了分析。我们在DLBCL和FL之间鉴定出294个差异修饰基因。DLBCL/FL分化基因中的差异5hmC与增强子标记H3K4me1和H3K27ac共定位。一个四基因组合（CNN2、HMG20B、ACRBP、IZUMO1）有力地代表了区分FL与DLBCL的总体5hmC修饰模式，在测试集中曲线下面积为88.5%。特征基因中的5hmC修饰水平中位数显示出区分患者全因死亡风险的潜力。这项研究提供了证据，表明cfDNA中的全基因组5hmC谱在DLBCL和FL之间存在差异，并且可以作为一种非侵入性方法加以利用。
