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Genomic Instability in Circulating Tumor Cells
Open AccessFeature PaperArticle

Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study

1
Biopathologie et Génétique des Cancers, Institute d’Analyse Médicale Imagenome, Inovie, 6 Rue Fontenille, 34000 Montpellier, France
2
Department of Pathology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
3
Oncologie Médicale, Clinique Clémenville, 25 rue Clémenville, 34000 Montpellier, France
4
Department of Pulmonary Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
5
Oncologie Médicale, Institute Sainte Catherine, 250 Chemin de Baigne Pieds, 84918 Avignon, France
6
Laboratoire de Cellules Rares Circulantes, University Medical Center of Montpellier, 641, Avenue du Doyen Gaston GIRAUD, 34093 Montpellier, France
*
Author to whom correspondence should be addressed.
Both authors contributed equally.
Both senior authors contributed equally.
Cancers 2020, 12(10), 3002; https://doi.org/10.3390/cancers12103002
Received: 23 September 2020 / Revised: 14 October 2020 / Accepted: 15 October 2020 / Published: 16 October 2020
(This article belongs to the Special Issue Biomarkers in Lung Cancer)
We compared the UltraSEEK™ Lung Panel on the MassARRAY® System (Agena Bioscience) with the FDA-approved Cobas® EGFR Mutation Test v2 for the detection of EGFR mutations in liquid biopsies of NSCLC patients, accompanied with preanalytical sample assessment using the novel Liquid IQ® Panel. For the detection of relevant predictive mutations using the UltraSEEK™ Lung Panel, an input of over 10 ng showed 100% concordance with Cobas® EGFR Mutation Test v2 and detection of all tissue confirmed mutations. In case of lower ccfDNA input, the risk of missing clinically relevant mutations should be considered. The use of a preanalytical ccfDNA quality control assay such as the Liquid IQ® Panel is recommended to confidently interpret results, avoiding bias induced by non-specific genomic DNA and low input of specific tumoral ccfDNA fragments.
Plasma-based tumor mutational profiling is arising as a reliable approach to detect primary and therapy-induced resistance mutations required for accurate treatment decision making. Here, we compared the FDA-approved Cobas® EGFR Mutation Test v2 with the UltraSEEK™ Lung Panel on the MassARRAY® System on detection of EGFR mutations, accompanied with preanalytical sample assessment using the novel Liquid IQ® Panel. 137 cancer patient-derived cell-free plasma samples were analyzed with the Cobas® and UltraSEEK™ tests. Liquid IQ® analysis was initially validated (n = 84) and used to determine ccfDNA input for all samples. Subsequently, Liquid IQ® results were applied to harmonize ccfDNA input for the Cobas® and UltraSEEK™ tests for 63 NSCLC patients. The overall concordance between the Cobas® and UltraSEEK™ tests was 86%. The Cobas® test detected more EGFR exon19 deletions and L858R mutations, while the UltraSEEK™ test detected more T790M mutations. A 100% concordance in both the clinical (n = 137) and harmonized (n = 63) cohorts was observed when >10 ng of ccfDNA was used as determined by the Liquid IQ® Panel. The Cobas® and UltraSEEK™ tests showed similar sensitivity in EGFR mutation detection, particularly when ccfDNA input was sufficient. It is recommended to preanalytically determine the ccfDNA concentration accurately to ensure sufficient input for reliable interpretation and treatment decision making. View Full-Text
Keywords: non-small cell lung cancer; EGFR mutation; circulating DNA; tyrosine kinase inhibitors; liquid biopsy non-small cell lung cancer; EGFR mutation; circulating DNA; tyrosine kinase inhibitors; liquid biopsy
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MDPI and ACS Style

Lamy, P.-J.; van der Leest, P.; Lozano, N.; Becht, C.; Duboeuf, F.; Groen, H.J.M.; Hilgers, W.; Pourel, N.; Rifaela, N.; Schuuring, E.; Alix-Panabières, C. Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study. Cancers 2020, 12, 3002.

AMA Style

Lamy P-J, van der Leest P, Lozano N, Becht C, Duboeuf F, Groen HJM, Hilgers W, Pourel N, Rifaela N, Schuuring E, Alix-Panabières C. Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study. Cancers. 2020; 12(10):3002.

Chicago/Turabian Style

Lamy, Pierre-Jean; van der Leest, Paul; Lozano, Nicolas; Becht, Catherine; Duboeuf, Frédérique; Groen, Harry J.M.; Hilgers, Werner; Pourel, Nicolas; Rifaela, Naomi; Schuuring, Ed; Alix-Panabières, Catherine. 2020. "Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study" Cancers 12, no. 10: 3002.

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