Cancer Methylation Dynamics Tracked With Cell-Free DNA in Blood

Stanford University researchers reporting in Genome Medicine explore epigenetic patterns in blood-based, cell-free DNA, focusing on single-molecule methylation patterns found by Oxford Nanopore sequencing of circulating tumor DNA. Using an optimized nanopore sequencing approach that involved a PCR-free and cytosine conversion-free library preparation process, the team initially characterized cell-free DNA (cfDNA) patterns on samples from 23 individuals with cancer and five unaffected control individuals. From there, they turned their attention to 20 colorectal cancer patients and longitudinal samples collected from gastrointestinal cancer or metastatic cancer patients over time, before putting together a classifier to link the methylation sequence reads to tumor or immune cells. "Our work demonstrated streamlined methylation analysis of cfDNA with significantly fewer experimental procedures and bottlenecks than short-read sequencing," the authors report, noting that the strategy "has the potential to impact liquid biopsy diagnostics for cancer detection and characterization."