TY - JOUR T1 - 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages JF - bioRxiv DO - 10.1101/162081 SP - 162081 AU - Chun-Xiao Song AU - Senlin Yin AU - Li Ma AU - Amanda Wheeler AU - Yu Chen AU - Yan Zhang AU - Bin Liu AU - Junjie Xiong AU - Weihan Zhang AU - Jiankun Hu AU - Zongguang Zhou AU - Biao Dong AU - Zhiqi Tian AU - Stefanie S. Jeffrey AU - Mei-Sze Chua AU - Samuel So AU - Weimin Li AU - Yuquan Wei AU - Jiajie Diao AU - Dan Xie AU - Stephen R. Quake Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/12/162081.abstract N2 - 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.One Sentence Summary Analyzing the epigenetic modification 5-hydroxymethylcysoine in circulating cell-free DNA reveals tumor tissue of origin and stages for cancer diagnostics. ER -