TABLE 8.
Comparison of Various and Most Current Versions of Guardant360 and Foundation Medicine FoundationACT Liquid Biopsy Platforms (as of December 31, 2017)
| Guardant360 54-Gene Panel | Guardant360 68-Gene Panel | Guardant360 70-Gene Panel | Guardant360 73-Gene Panel*71 | Foundation Medicine FoundationACT 62-Gene Panel*72 | |
|---|---|---|---|---|---|
| Commercial Launch Date | June 2014 | August 2015 | October 2015 | November 2016 | June 2016 |
| Amount of Blood Needed | Two 10-mL Streck tubes | Two 10-mL Streck tubes | Two 10-mL Streck tubes | Two 10-mL Streck tubes | Two 10-mL tubes (Foundation ACT Specimen Collection Kit) |
| Minimal Amount of Cell-Free DNA | > 5 ng of cell-free DNA1 | > 5 ng of cell-free DNA1 | > 5 ng of cell-free DNA1 | > 5 ng of cell-free DNA1 | ≥ 20 ng of cell-free DNA |
| Methods for Isolating ctDNA | QIAamp circulating nucleic acid kit (Qiagen) | QIAamp circulating nucleic acid kit (Qiagen) | QIAamp circulating nucleic acid kit (Qiagen) | QIAamp circulating nucleic acid kit (Qiagen) | |
| Types of Alterations Analyzed and No. of Genes | Complete exons (18 genes) | Complete exons (29 genes) | Complete exons (30 genes) | Complete exons (19 genes)** | Complete exons (27 genes) |
| Critical exons (36 genes) | Critical exons (39 genes) | Critical exons (40 genes) | Critical exons (54 genes) | Critical exons (33 genes) | |
| CNV (3 genes) | Indel (1 gene) | Indels (3 genes) | Indels (23 genes) | Indel (27genes) | |
| CNV (16 genes) | CNV (18 genes) | CNV (18 genes) | Amplification (27 genes) | ||
| Fusions (4 genes) | Fusions (6 genes)† | Fusions (6 genes)† | Fusions (6 genes)†‡ Promoter region only (TERT) |
||
| Sequencing Platform | HiSEquation 2500 (lllumina)l, 2 | HiSeq 2500 or NextSEquation 500 (lllumina) | HiSeq 2500 or NextSEquation 500 (lllumina) | HiSeq 2500 or NextSEquation 500 (lllumina) | HiSeq 2500 or HiSeq 4000 (lllumina) |
| Depth of Coverage | ?10,000× (average raw) | ~15,000×(average raw) | 7,503× (median, unique, actual depth of coverage reported) | ||
| Single-Nucleotide Variation | Varies between < 0.1% and 0.1%; depends on particular gene | Varies between < 0.1% and 0.1%; depends on particular gene | Varies between < 0.1% and 0.1%; depends on particular gene | ≥ 0.04%; ≥ 0.25%, sensivitiy 100%, PPV 99.2%; 0.05–0.25% sensitivity 63.8%, PPV 96.3% | ≥ 0.1% (0.1%–0.5%; sensitivity, 67.3%;PPV, 93.6%) ≥ 0.05% (sensitivity > 98.9%; PPV > 99.9%) |
| Indel | Varies between < 0.1% and 0.1%; depends on particular gene | Varies between < 0.1% and 0.1%; depends on particular gene | Varies between < 0.1% and 0.1%; depends on particular gene | ≥ 0.02%; ≥ 0.02%, sensitivity 100%, PPV 98.2%; 0.05–0.2% sensitivity 67.8%, PPV 98.2% | ≥ 1% (sensitivity, 99.9%; PPV, 98.8%) |
| CNV/Amplification | Varies between < 0.1% and 0.1%; depends on particular gene | Varies between < 0.1% and 0.1%; depends on particular gene | Varies between < 0.1% and 0.1%; depends on particular gene | ≥ 2.12 copies | ≥ 20% (sensitivity, 95.3%; PPV, 97.5%) |
| Fusions/Rearrangement | Varies between < 0.1% and 0.1%; depends on particular gene | Varies between < 0.1% and 0.1%; depends on particular gene | ≥ 0.04%; ≥ 0.2% sensitivity 95%, PPV 100%; 0.05–0.2% sensitivity 83%, PPV 100% | ≥ 1% (sensitivity > 99.9%; PPV, 98.8%) < 1% (sensitivity, 86.8%; PPV > 99%) |
|
| Turnaround Time for Results | Within 2 wk of receiving blood sample | Median of 7 calendar days of receiving blood sample | Within 2 wk of receiving blood sample | ||
| Difference in Gene Panel | ABL, CSF1R, ERBB4, FLT3, KDR (VEGFR2), PROC, RB1, and SMARCB1 genes were deleted and replaced with ARAF, ARID1A, BRCA1, BRCA2, CCND1, CCND2, CCNE1, CDK4, CDK6, CDKN2B, ESR1, GATA3, MAP2K1, MAP2K2, NF1, NTRK1, NTRK3, NFE2L2, RHEB, RHOA, RIT1, RAF1, and ROS1 genes. Copy number amplification calling increased from 3 to 16 genes (added AR, BRAF, CCND1, CCND2, CCNE1, CDK4, CDK6, FGFR1, FGFR2, KIT, KRAS, MYC, PDGFRA, PIK3CA, RAF1J Fusing calling added for 4 genes (ALK, ROS1, RET, NTRK1). Indel calling added for EGFR (exon 19/20) | RB1 and TSC1 genes were added; number of fusions detected increased from 4 to 6 (additional FGFR2 and FGFR3 fusion detection). Indel coverage for ERBB2 (exon 19/20) and MET exon 14 splice site variants wasadded | SRC and CDKN2B were deleted from panel and DDR2, MAP-K1(ERK2), MAPK3 (ERK1), MTOR, and NTRK3 were added. Copy number amplification calling was increased to 18 genes (CCND1, CCND2). Indel coverage expanded from 3 to 23 genes (ATM, APC, ARID1A,BRCA1, BRCA2, CDH1,CDKN2A, GATA3, KIT, MLH1,MTOR, NF1, PDGFRA, PTEN, RB1,SM AD4,ST-K11,TP53,TSC1,VHL) | NA | |
| Cost | NA | NA | NA | $5,800 per test ($5,000 suggested contracted price per test) | $5,800 USD per test (contracted price may vary) |
| References (Selected Clinical Use of One Particular Platform) | 73–76 | 75–79 | 64,75,76,80,81 | 82,83 | 84–87 |
Although the difference in the number of genes is 11 between the current Guardant360 and Foundation Medicine FoundationACT, the actual difference in the number of genes analyzed is 31 because of unique genes analyzed by each liquid biopsy. Twenty-one genes were unique to Guardant360: AR, ARID1A, ATM, FBXW7, GATA3, HNF1A, MAPK3, MLH1, MPL, NFE2L2, NOTCH1, NTRK1, NTRK3, RB1, RHEB, THOA, RIT1, SMAD, STK11, TSC1, VHL. Ten genes were unique to Foundation Medicine FoundationACT: ABL, BTK, CRKL, ERRFI1, FOXL2, MDM2, MYD88, PDGFR-beta, PD-L2, VEGF-alpha.
The 19 genes that have complete exon coverage in the Guardant 73-gene panel are as follows: APC, AR, BRAF, BRAC1, BRCA2, EGFR, ERBB2, HRAS, KRAS, NRAS, KIT, MAPK1(ERK2), MAPK2 (ERK1), MET, MYC, PIK3CA, RB1, TP53, STK11. Underlined genes have complete exon coverage by Foundation Medicine FoundationACT.
Both Guardant and Foundation Medicine FoundationACT report four common fusions: ALK, ROS1, RET, and FGFR3 fusions. Guardant360 also reports additional NTRK1 and FGFR2 fusions, and Foundation Medicine FoundationACT reports additional EGFR and PDGFR-alpha fusions.
ROS1 rearrangement is the only ROS1 alteration detected by the current version of Foundation Medicine FoundationACT.
Abbreviations: PPV, positive predictive value; NA, not available; USD, US dollars.