Noninvasive diagnosis of actionable mutations by deep sequencing of circulating free DNA in lung cancer from never-smokers: a proof-of-concept study from BioCAST/IFCT-1002
Published version of a preprint
Abstract
PURPOSE: Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations. EXPERIMENTAL DESIGN: A total of 107 plasma samples were collected from the BioCAST/IFCT-1002 lung cancer study (never-smokers cohort). Matched tumor DNA (tDNA) was obtained for 68 cases. Multiplex PCR-based assays were designed to target specific coding regions in EGFR, KRAS, BRAF, ERBB2, and PI3KCA genes, and amplicon sequencing was performed at deep coverage on the cfDNA/tDNA pairs using the NGS IonTorrent Personal Genome Machine Platform. RESULTS: CfDNA concentration in plasma was significantly associated with both stage and number of metastatic sites. In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. Sensitivity of the test was 58% (95% confidence interval, 43%-71%) and the estimated specificity was 87% (62%-96%). CONCLUSION: These data demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of a range of tumor biomarkers in patients with metastatic lung cancer.
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No co-expression of EGFR and KRAS mutations was found in any plasma samples.
“Consistent with prior reports, we found no co-expression of EGFR and KRAS mutations in any plasma samples (23, 39).”
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References 52 · Cited by 215
- Authors
- Couraud, S., Vaca-Paniagua, F., Villar, S., Oliver, J., Schuster, T., Blanché, H., Girard, N., Trédaniel, J., Guilleminault, L., Gervais, R., Prim, N., Vincent, M., Margery, J., Larivé, S., Foucher, P., Duvert, B., Vallee, M., Le Calvez-Kelm, F., McKay, J., Missy, P., Morin, F., Zalcman, G., Olivier, M., & Souquet, P.-J.
- Affiliations
- Lyon 1 Université (FR)
- 1International Agency for Research on Cancer, Section of Mechanisms of Carcinogenesis, Molecular Mechanisms and Biomarkers Group, Lyon Cedex, France.
- Centre international de recherche sur le cancer (FR)
- Jewish General Hospital (CA)
- Fondation Jean Dausset-CEPH (FR)
- Sorbonne Paris Cité (FR)
- Université de Tours (FR)
- Centre François Baclesse (FR)
- Hôpitaux Universitaires de Strasbourg (FR)
- Centre Hospitalier Saint-Joseph Saint-Luc (FR)
- Hôpital d'instruction des Armées Percy (FR)
- 18Department of Pulmonology, Mâcon Hospital, Mâcon, France.
- CHU Dijon Bourgogne (FR)
- 20Department of Oncology, Montélimar Hospital, Montélimar, France.
- 6International Agency for Research on Cancer, Genetic Cancer Susceptibility Group, Lyon Cedex, France.
- Intergroupe Francophone de Cancérologie Thoracique (FR)
- Inserm (FR)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2014-09-01
- Volume
- 20
- Issue
- 17
- Pages
- 4613-4624
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2112598101
- Cited by
- 215
- References
- 52
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 10 · 2022: 8 · 2021: 21 · 2020: 21 · 2019: 18 · 2018: 30 · 2017: 31 · 2016: 38 · 2015: 24 · 2014: 5
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- World Health Organization
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- cell-free DNA, liquid biopsy, metastatic lung cancer, never smokers, actionable mutations, EGFR, KRAS, BRAF, ERBB2, PIK3CA, mutation detection sensitivity and specificity, tumor markers
- MeSH terms
- Adult, Aged, DNA Mutational Analysis, DNA, Neoplasm, Female, Humans, Lung Neoplasms, Middle Aged, Neoplastic Cells, Circulating, Proto-Oncogene Proteins, Smoking, Biomarkers, Tumor, Proto-Oncogene Proteins p21(ras), ras Proteins, Erb-b2 Receptor Tyrosine Kinases, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins B-raf, Class I Phosphatidylinositol 3-Kinases, High-Throughput Nucleotide Sequencing, ErbB Receptors
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