Methylomics and Fragmentomics: Pioneering Cancer Detection Models

Hanlee Ji from Stanford University presented at London Calling 2024 on “Genomic sequencing for characterizing tumor minimal residual disease versus early cancer.” Ji spoke about apoptosis and circulating tumor DNA. Ji and the team evaluated the recurrence of metastatic colorectal cancer with circulating DNA monitoring. Early detection of breast cancer can benefit from nanopore sequencing with circulating tumor DNA (ctDNA). The native detection of DNA methylation and fragmentation patterns of cell-free DNA are advantages of nanopore sequencing. Genome-wide methylation patterns in cancer can now be obtained through cell-free DNA fragments. Nucleosome structure can be determined through the DNA fragmentation patterns. Ji explained that the insert size can help determine the patterns of nucleosomes. Ji’s team determined that cfDNA fragmentation patterns may be biologically relevant and that cell-free DNA (cfDNA) is highly enriched in monosomes. No enrichment is necessary. A highly optimized DNA extraction procedure is followed, and the sample is sequenced using an Oxford Nanopore PromethION. Ji explained that they found methylation signatures in ctDNA. They have performed this as a way of doing longitudinal monitoring. Ji and colleagues created a series of early-stage breast cancer detection models with high sensitivity and accuracy. Ji mentioned that early breast cancer detection with methylomics and fragmentomics is becoming more mainstream. While I don’t work on cancer, I appreciate the power and potential of this approach. It also makes me wonder if bacteria have methylation patterns for different biofilm stages.

How can cell-free DNA be used for early detection of cancer? AI-generated image.