Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring.

ABSTRACT: In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole-genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10^-5. The WGS approach enabled dynamic tumor burden tracking and postoperative residual disease detection, associated with

SUBMITTER: Zviran A 

PROVIDER: S-EPMC8108131 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature