Toward the Early Detection of Cancer by Decoding the Epigenetic and Environmental Fingerprints of Cell-Free DNA

Cancer Cell. 2019 Oct 14;36(4):350-368. doi: 10.1016/j.ccell.2019.09.003.

Abstract

Widespread adaptation of liquid biopsy for the early detection of cancer has yet to reach clinical utility. Circulating tumor DNA is commonly detected though the presence of genetic alterations, but only a minor fraction of tumor-derived cell-free DNA (cfDNA) fragments exhibit mutations. The cellular processes occurring in cancer development mark the chromatin. These epigenetic marks are reflected by modifications in the cfDNA methylation, fragment size, and structure. In this review, we describe how going beyond DNA sequence information alone, by analyzing cfDNA epigenetic and immune signatures, boosts the potential of liquid biopsy for the early detection of cancer.

Keywords: cancer; cell-free DNA; chromatin; circulating tumor DNA; epigenetic; exosome; fragmentation; liquid biopsy; methylation; mutation; vesicle.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Chromatin / genetics
  • Circulating Tumor DNA / analysis*
  • Circulating Tumor DNA / genetics
  • DNA Methylation
  • Early Detection of Cancer / methods*
  • Epigenesis, Genetic
  • Epigenomics / methods
  • Humans
  • Liquid Biopsy / methods
  • Mutation
  • Neoplasms / blood
  • Neoplasms / diagnosis*
  • Neoplasms / genetics
  • Neoplasms / urine
  • Sequence Analysis, DNA / methods

Substances

  • Biomarkers, Tumor
  • Chromatin
  • Circulating Tumor DNA