Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection

We used a highly sensitive nano-5hmC-Seal method and profiled the genome-wide distribution of 5-hydroxymethylcytosine (5hmC) in plasma cell-free DNA (cfDNA) from 384 patients with bladder, breast, colorectal, kidney, lung, or prostate cancer and 221 controls. We used machine learning and developed plasma cfDNA 5hmC signatures that are highly sensitive for cancer detection and cancer origin determination. We also identified genes and signaling pathways with aberrant DNA hydroxymethylation in six cancers. Overall design: Analyze 5-hydroxymethyl cytosine (5hmC) genome-wide distribution in plasma cell-free DNA from bladder, breast, colorectal, kidney, lung, and prostate cancer patients in comparison to non-cancer controls