Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin
Open accessAbstract
As availability of precision therapies expands, a well-validated circulating cell-free DNA (cfDNA)-based comprehensive genomic profiling assay has the potential to provide considerable value as a complement to tissue-based testing to ensure potentially life-extending therapies are administered to patients most likely to benefit. Additional data supporting the clinical validity of cfDNA-based testing is necessary to inform optimal use of these assays in the clinic. The FoundationOne®Liquid CDx assay is a pan-cancer cfDNA-based comprehensive genomic profiling assay that was recently approved by FDA. Validation studies included >7,500 tests and >30,000 unique variants across >300 genes and >30 cancer types. Clinical validity results across multiple tumor types are presented. Additionally, results demonstrated a 95% limit of detection of 0.40% variant allele fraction for select substitutions and insertions/deletions, 0.37% variant allele fraction for select rearrangements, 21.7% tumor fraction for copy number amplifications, and 30.4% TF for copy number losses. The limit of detection for microsatellite instability and blood tumor mutational burden were also determined. The false positive variant rate was 0.013% (approximately 1 in 8,000). Reproducibility of variant calling was 99.59%. In comparison with an orthogonal method, an overall positive percent agreement of 96.3% and negative percent agreement of >99.9% was observed. These study results demonstrate that FoundationOne Liquid CDx accurately and reproducibly detects the major types of genomic alterations in addition to complex biomarkers such as microsatellite instability, blood tumor mutational burden, and tumor fraction. Critically, clinical validity data is presented across multiple cancer types.
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ctDNA sequencing was done in a CLIA-certified and CAP-accredited laboratory using the validated, FDA-approved F1LCDx next-generation sequencing panel.
“ctDNA sequencing was performed in a CLIA-certified, College of American Pathologists–accredited laboratory (Foundation Medicine), using the validated, FDA-approved NGS panel assay F1LCDx.20”
From Clinical Liquid Biopsy Testing for Detection of Actionable Genomic Alterations in Children and Young Adults With Advanced Solid Tumors on the GAIN Study (2026) · cites this paper as [20]
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- Authors
- Woodhouse, R., Li, M., Hughes, J., Delfosse, D., Skoletsky, J., Ma, P., Meng, W., Dewal, N., Milbury, C., Clark, T., Donahue, A., Stover, D., Kennedy, M., Dacpano-Komansky, J., Burns, C., Vietz, C., Alexander, B., Hegde, P., & Dennis, L.
- Affiliations
- Foundation Medicine (United States) (US)
- Novartis (United States) (US)
- Corresponding author
- Woodhouse, Ryan
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2020-09-25
- Volume
- 15
- Issue
- 9
- Pages
- e0237802
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W3088519161
- Cited by
- 516
- References
- 44
- Citations by year
- 2026: 82 · 2025: 119 · 2024: 91 · 2023: 99 · 2022: 79 · 2021: 44 · 2020: 2
- FWCI
- 19.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Foundation Medicine
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- FoundationOne Liquid CDx, cell-free DNA, liquid biopsy, comprehensive genomic profiling, solid tumors, clinical validation, variant allele frequency, tumor fraction, microsatellite instability, tumor mutational burden, copy number alterations, precision oncology
- MeSH terms
- Cell-Free Nucleic Acids, Progression-Free Survival, Biological Assay, Exons, Humans, Mutation, Neoplasms, Reproducibility of Results, Genomics, Limit of Detection, Class I Phosphatidylinositol 3-Kinases, ErbB Receptors
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