5-Hydroxymethylcytosine profiling from genomic and cell-free DNA for colorectal cancers patients
5-Hydroxymethylcytosine profiling from genomic and cell-free DNA for colorectal cancers patients
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结直肠癌患者基因组和游离 DNA 的 5-羟甲基胞嘧啶分析
DOI：
10.1111/jcmm.14252
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发表时间：
2019-05-01
影响因子：
5.3
通讯作者：
Zhou, Pinghong
中科院分区：
文献类型：
--
作者：
Gao, Pingting;Lin, Shengli;Zhou, Pinghong
5-羟甲基胞嘧啶（5 hmC）是一种DNA修饰，由10 - 11易位（泰特）家族酶催化的反应中5-甲基胞嘧啶（5 mC）氧化产生。它往往标志着基因激活，并影响一系列发育和疾病相关的生物过程。在这篇手稿中，我们提出了一个5 hmC选择性化学标记技术（hmC-Seal）捕获和测序含有5 hmC的DNA片段与低输入。我们测试了10个肿瘤/邻近结肠癌组织和10个肿瘤/健康血浆样品。此外，我们测试了这种方法是否可以从血浆中产生癌症患者、健康对照和癌前腺瘤患者之间的5 hmC差异基因。针对结肠癌鉴定了稳健的癌症特异性表观遗传特征。结果表明，5 hmC主要分布在基因活性区。本研究结果还表明，5 hmC变化信号在结肠癌的早期诊断，甚至在癌前腺瘤的诊断中有潜在的应用价值。我们证明了5 hmC-Seal方法在作为潜在生物标志物的组织和无细胞DNA（cfDNA）中的稳健性。本研究为5 hmC-Seal方法在结直肠癌早期诊断中的应用提供了潜在的价值和可行性。我们相信这种策略可能是一种有效的基于液体活检的诊断和使用cfDNA的结肠癌的潜在预后方法。
5-Hydroxymethylcytosine (5hmC) is a DNA modification that is generated by the oxidation of 5-methylcytosine (5mC) in a reaction catalyzed by the ten-eleven translocation (TET) family enzymes. It tends to mark gene activation and affects a spectrum of developmental and disease-related biological processes. In this manuscript, we present a 5hmC selective chemical labelling technology (hmC-Seal) to capture and sequence 5hmC-containing DNA fragments with low input. We tested 10 tumour/adjacent colon cancer tissues and 10 tumour/healthy plasma samples. Furthermore, we tested if this methodology could generate the 5hmC differential genes among cancer patients, healthy controls and precancerous adenoma patients from plasma. Robust cancer-specific epigenetic signatures were identified for colon cancers. The results show that 5hmC is mainly distributed in gene active regions. The results also indicate the potential application of 5hmC change signals in early stage of colon cancer, even show potential in the diagnosis of precancerous adenoma. We demonstrated the robustness of the 5hmC-Seal method in tissue and cell-free DNA (cfDNA) as potential biomarkers. Moreover, this study provides the potential value and feasibility of 5hmC-Seal approach on colorectal cancer (CRC) early detection. We believe this strategy could be an effective liquid biopsy-based diagnosis and a potential prognosis method for colon cancer using cfDNA.