机构：[1]Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA[2]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and National Collaborative Innovation Center, Chengdu, Sichuan 610041, China四川大学华西医院[3]Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China四川大学华西医院[4]Asian Liver Center, Stanford University School of Medicine, Stanford, CA 94305, USA[5]Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA[6]Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China四川大学华西医院[7]Department of Pulmonary Tumor Ward, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, China四川省肿瘤医院[8]Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China四川大学华西医院[9]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China四川大学华西医院[10]Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA[11]Center of Precision Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China四川大学华西医院[12]Chan Zuckerberg Biohub, San Francisco, CA 94518, USA[13]Ludwig Institute for Cancer Research and Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31571327, 91631111]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [U01 CA154209]; Department of DefenseUnited States Department of Defense [W81XWH1110287]
第一作者机构：[1]Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA[13]Ludwig Institute for Cancer Research and Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
共同第一作者：
通讯作者：
通讯机构：[1]Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA 94305, USA[2]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and National Collaborative Innovation Center, Chengdu, Sichuan 610041, China[9]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China[11]Center of Precision Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China[12]Chan Zuckerberg Biohub, San Francisco, CA 94518, USA
推荐引用方式(GB/T 7714)：
Chun-Xiao Song,Senlin Yin,Li Ma,et al.5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages[J].CELL RESEARCH.2017,27(10):1231-1242.doi:10.1038/cr.2017.106.
APA：
Chun-Xiao Song,Senlin Yin,Li Ma,Amanda Wheeler,Yu Chen...&Stephen R Quake.(2017).5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages.CELL RESEARCH,27,(10)
MLA：
Chun-Xiao Song,et al."5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages".CELL RESEARCH 27..10(2017):1231-1242
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