Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing

TLDR

Genome‑wide hypomethylation is frequently observed in cancers. We demonstrate that plasma bisulfite sequencing of genome‑wide hypomethylation can sensitively and specifically detect multiple cancers, monitor post‑treatment patients, and simultaneously identify copy‑number aberrations, enabling synergistic enhancement of diagnostic accuracy at low sequencing depth.

Abstract

Significance Genome-wide hypomethylation is frequently observed in cancers. In this study, we showed that genome-wide hypomethylation analysis in plasma using shotgun massively parallel bisulfite sequencing is a powerful general approach for the detection of multiple types of cancers. This approach is particularly attractive because high sensitivity and specificity can be achieved using low sequence depth, which is practical diagnostically. This approach can also be used for monitoring patients following treatment. The same sequencing data can be further used for detecting cancer-associated copy number aberrations at no additional costs. One could thus combine plasma hypomethylation and copy number analyses in a synergistic manner for further enhancing detection sensitivity or specificity.