Many cell-free DNA (cfDNA) mutations are derived from clonal hematopoiesis: Implications for interpretation of liquid biopsy tests


  • A large fraction of cell-free DNA (cfDNA) fragments are known to be derived from hematopoietic cells (Lui 2002).
  • Sequencing of genomic DNA (gDNA) from white blood cells (WBC) in circulation has revealed an age-dependent presence of clones carrying somatic variants—a phenomenon now termed clonal hematopoiesis (Genovese 2014).
  • Somatic alterations in cfDNA can be tumor-derived but also could represent somatic changes associated with clonal hematopoiesis.
  • We applied a high-intensity sequencing approach (ultra-deep sequencing with broad genomic coverage) to characterize both cfDNA and WBC gDNA from cancer and non-cancer subjects.