DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.

中文翻译：

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循环无细胞DNA中的5-羟甲基胞嘧啶签名作为人类癌症的诊断生物标志物

DNA修饰（例如5-甲基胞嘧啶（5mC）和5-羟甲基胞嘧啶（5hmC））是表观遗传标记，已知会影响哺乳动物的整体基因表达。鉴于它们在人类基因组中的普遍性，与基因表达的密切相关性和高度的化学稳定性，这些DNA表观遗传标记可以作为癌症诊断的理想生物标记。利用高度敏感和选择性的化学标记技术，我们在这里报告了从260个队列中收集的配对肿瘤和邻近组织的循环无细胞DNA（cfDNA）和基因组DNA（gDNA）中5hmC的全基因组分布图最近被确诊患有结肠直肠癌，胃癌，胰腺癌，肝癌或甲状腺癌和正常组织的90名健康患者的患者。5hmC主要分布在与开放染色质和允许的组蛋白修饰一致的转录活性区域中。在cfDNA中鉴定出了与癌症相关的强大的5hmC信号特征，这些特征是特定癌症类型的特征。循环cfDNA的基于5hmC的生物标记物可高度预测结直肠癌和胃癌，并且优于传统的生物标记物，并且与组织活检中的5hmC的生物标记物相当。因此，这种新策略可能会导致开发有效的，微创的方法，通过对血液样本的分析来诊断和预后癌症。基于5hmC的循环cfDNA生物标志物可高度预测结直肠癌和胃癌，并且优于常规生物标志物，可与组织活检中的5hmC生物标志物相媲美。因此，这种新策略可能会导致开发有效的，微创的方法，通过对血液样本的分析来诊断和预后癌症。基于5hmC的循环cfDNA生物标志物可高度预测结直肠癌和胃癌，并且优于常规生物标志物，可与组织活检中的5hmC生物标志物相媲美。因此，这种新策略可能会导致通过对血液样本进行分析来开发有效的，微创的方法来诊断和预后癌症。