5-Hydroxymethylcytosine (5hmC) is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA (cfDNA) using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell-free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome. Our proof-of-principle results suggest that cell-free 5hmC signatures may potentially be used not only to identify cancer types but also to track tumor stage in some cancers.

中文翻译：

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无细胞DNA中的5-羟甲基胞嘧啶特征提供了有关肿瘤类型和阶段的信息。

5-羟甲基胞嘧啶（5hmC）是一种重要的哺乳动物DNA表观遗传修饰，已与基因调控和癌症发病机理相关。在这里，我们使用基于化学标记的低投入shot弹枪测序方法，探索了5hmC在循环无细胞DNA（cfDNA）中的诊断潜力。我们对来自7种不同癌症类型的49名患者的无细胞5hmC进行了测序，发现了可用于准确预测癌症类型和分期的独特特征。具体而言，我们发现肺癌导致cfDNA中5hmC的进行性整体丢失，而肝细胞癌和胰腺癌则导致无细胞羟甲基基因组的疾病特异性变化。