@article{ea9fa4c7a21c4ad6abeca7cab6c4dafe,
title = "5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers",
abstract = "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.",
keywords = "5-hydroxymethylcytosine, 5hmC-Seal, cancer biomarker, circulating cell-free DNA, liquid biopsy",
author = "Wenshuai Li and Xu Zhang and Xingyu Lu and Lei You and Yanqun Song and Zhongguang Luo and Jun Zhang and Ji Nie and Wanwei Zheng and Diannan Xu and Yaping Wang and Yuanqiang Dong and Shulin Yu and Jun Hong and Jianping Shi and Hankun Hao and Fen Luo and Luchun Hua and Peng Wang and Xiaoping Qian and Fang Yuan and Lianhuan Wei and Ming Cui and Taiping Zhang and Quan Liao and Menghua Dai and Ziwen Liu and Ge Chen and Katherine Meckel and Sarbani Adhikari and Guifang Jia and Bissonnette, {Marc B.} and Xinxiang Zhang and Yupei Zhao and Wei Zhang and Chuan He and Jie Liu",
note = "Funding Information: This work was supported in part, by grants from the National Institutes of Health (U01CA217078 to MBB and WZ, R33CA225338 to CH and WZ, P30CA060553 Career Development Fund to WZ, R01HG006827 to CH), The University of Chicago Ludwig Center for Metastasis Research (to CH), and the Research Special Fund for Public Welfare Industry of Health (201402001 to YZ). We thank Dr H Pickersgill (Life Science Editors) for editing this manuscript. Funding Information: 1Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China; 2Section of Hematology/Oncology, Department of Medicine,University of Illinois, Chicago, IL 60612, USA; 3Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA; 4Shanghai Epican Genetech, Co. Ltd., Zhangjiang Hi-Tech Park, Shanghai 201203, China; 5Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China; 6Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China; 7Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China; 8Department of Digestive Diseases, Pudong Hospital, Fudan University, Shanghai 201399, China; 9Department of Oncology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China; 10Beijing National Laboratory for Molecular Sciences, College of Chemistry, Peking University, Beijing 100871, China; 11Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; 12Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; 13Department of Chemical Biology, Structure and Function Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; 14Department of Preventive Medicine and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; 15Department of Immunology, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = oct,
day = "1",
doi = "10.1038/cr.2017.121",
language = "English (US)",
volume = "27",
pages = "1243--1257",
journal = "Cell Research",
issn = "1001-0602",
publisher = "Nature Publishing Group",
number = "10",
}
