Table 1

Current cell-free DNA-based approaches for the detection of cancer

ApproachMethodologyRelative abundance of target signalsAssayNumber of targetsPerformanceCohort sizeTumor informedExtent of clinical evaluationRelative cost of approachReferences
Mutation analysisCapture-based targeted, multiplex PCR, genome-wide or whole-exome next generation sequencingFew to hundreds of known mutations or genome-wideElio Plasma Resolve33VAF≥95% LoD 0.1%–0.5%n=75NoClinical validity, case–control, prospective cohort$$$–$$$$ 32
FoundationOne Liquid324VAF≥95% LoD 0.4%n>30 cancer typesNo 12
LoD 0.25%
n>1500No 34
MRDetectGenome-wideVAF LoD 10−5, >85% at 20×, >99% at 50×n=98Yes 73
Signatera16VAF>95% LoD 0.01%n=49Yes 35 36
CancerSeek (DETECT-A)16Specificity: 98.9% Sensitivity: 27%n=9,911No 26
RaDaR48VAF=95% LoD 0.001%n=88, n=17Yes 37 38
DNA methylation profilingBisulfite conversion- sequencing or DNA methylation immunoprecipitation-sequencingThousands to tens of thousands of CpG methylation differencesGalleri (PATHFINDER)Targeted methylationSpecificity: 99.1% Sensitivity: 29%n=6,621NoClinical validity, case–control, prospective cohort$$$–$$$$ 81
cfMeDIP-seqAnti-5mcLung AUC: 0.971
AML AUC: 0.98
PDAC AUC: 0.92
n=388No 24 59
Fragmentation profilingLow-coverage whole-genome, next-generation sequencingMillions of fragmentation differencesDELFIGenome-wideAUC: 0.86 - 0.98 across cancer typesn=423NoProof-of-concept, clinical validity, case–control, prospective-retrospective cohort$–$$ 61–63
End MotifsMotif diversity scoreAUC 0.86n=89No 70
GALYFREGenome-wideSpecificity: 95%
Sensitivity: 66.9%
n=661No 71
Mutational signaturesGEMINIGenome-wideAUC 0.90n=109No 41
PointyGenome-wideAUC 0.96n=405No 42
  • AML, acute myeloid leukemia; AUC, area under the curve; LoD, limit of detection; PDAC, pancreatic ductal adenocarcinoma; VAF, variant allele fraction.