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The advent of next\u2010generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor\u2010derived materials. Researchers are now able to monitor the dynamics of tumorigenesis in new dimensions, such as using circulating cell\u2010free DNA (cfDNA) and tumor DNA (ctDNA). Mutation\u2010based assays in liquid biopsy cannot always provide consistent results across studies due partly to intra\u2010 and inter\u2010tumoral heterogeneity as well as technical limitations. In contrast, epigenetic analysis of patient\u2010derived cfDNA is a promising alternative, especially for early detection and disease surveillance, because epigenetic modifications are tissue\u2010specific and reflect the dynamic process of cancer progression. Therefore, cfDNA\u2010based epigenetic assays are emerging to be a highly sensitive, minimally invasive tool for cancer diagnosis and prognosis with great potential in future precise care of cancer patients. The major obstacle for applying epigenetic analysis of cfDNA, however, has been the lack of enabling techniques with high sensitivity and technical robustness. In this review, we summarized the advances in epigenome\u2010wide profiling of 5\u2010hydroxymethylcytosine (5hmC) in cfDNA, focusing on the detection approaches and potential role as biomarkers in different cancer types.<\/jats:p>","DOI":"10.1186\/s40880-019-0356-x","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T01:48:41Z","timestamp":1553824121000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Towards precision medicine: advances in 5\u2010hydroxymethylcytosine cancer biomarker discovery in liquid biopsy"],"prefix":"10.34133","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3520-3724","authenticated-orcid":false,"given":"Chang","family":"Zeng","sequence":"first","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Kunce","family":"Stroup","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.\u2010H.","family":"Chiu","sequence":"additional","affiliation":[{"name":"University of Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]},{"name":"Northwestern University Feinberg School of Medicine","place":["Chicago, USA"]},{"name":"Jining Medical University","place":["Jining, P. 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