PT  - JOURNAL ARTICLE
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
TI  - 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages
AID  - 10.1101/162081
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 162081
4099  - http://biorxiv.org/content/early/2017/07/12/162081.short
4100  - http://biorxiv.org/content/early/2017/07/12/162081.full
AB  - 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.