Abstract |
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.
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Authors | Chun-Xiao Song, Senlin Yin, Li Ma, Amanda Wheeler, Yu Chen, Yan Zhang, Bin Liu, Junjie Xiong, Weihan Zhang, Jiankun Hu, Zongguang Zhou, Biao Dong, Zhiqi Tian, Stefanie S Jeffrey, Mei-Sze Chua, Samuel So, Weimin Li, Yuquan Wei, Jiajie Diao, Dan Xie, Stephen R Quake |
Journal | Cell research
(Cell Res)
Vol. 27
Issue 10
Pg. 1231-1242
(Oct 2017)
ISSN: 1748-7838 [Electronic] England |
PMID | 28820176
(Publication Type: Journal Article)
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Chemical References |
- Cell-Free Nucleic Acids
- Circulating Tumor DNA
- 5-hydroxymethylcytosine
- 5-Methylcytosine
- Cytosine
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Topics |
- 5-Methylcytosine
(analogs & derivatives, blood)
- Adult
- Aged
- Animals
- Cell-Free Nucleic Acids
(blood)
- Circulating Tumor DNA
(blood)
- Cytosine
(blood)
- DNA Methylation
(genetics)
- Epigenesis, Genetic
- Female
- Humans
- Male
- Middle Aged
- Neoplasm Staging
- Neoplasms
(blood, classification, genetics, pathology)
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