Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring. Academic Article uri icon

Overview

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 adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome-wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance and empowering treatment optimization in low-disease-burden oncology care.

authors

publication date

  • June 1, 2020

Research

keywords

  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • DNA, Neoplasm
  • Neoplasms

Identity

PubMed Central ID

  • PMC8108131

Scopus Document Identifier

  • 85085878635

Digital Object Identifier (DOI)

  • 10.1038/s41591-020-0915-3

PubMed ID

  • 32483360

Additional Document Info

volume

  • 26

issue

  • 7