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- Title
Next-generation sequencing for tumor mutation quantification using liquid biopsies.
- Authors
Provencio, Mariano; Pérez-Barrios, Clara; Barquin, Miguel; Calvo, Virginia; Franco, Fabio; Sánchez, Estela; Sánchez, Ricardo; Marsden, Daniel; Cristóbal Sánchez, Juan; Martin Acosta, Paloma; Laza-Briviesca, Raquel; Cruz-Bermúdez, Alberto; Romero, Atocha
- Abstract
Background: Non-small cell lung cancer (NSCLC) patients benefit from targeted therapies both in first- and second-line treatment. Nevertheless, molecular profiling of lung cancer tumors after first disease progression is seldom performed. The analysis of circulating tumor DNA (ctDNA) enables not only non-invasive biomarker testing but also monitoring tumor response to treatment. Digital PCR (dPCR), although a robust approach, only enables the analysis of a limited number of mutations. Next-generation sequencing (NGS), on the other hand, enables the analysis of significantly greater numbers of mutations. Methods: A total of 54 circulating free DNA (cfDNA) samples from 52 NSCLC patients and two healthy donors were analyzed by NGS using the Oncomine™ Lung cfDNA Assay kit and dPCR. Results: Lin's concordance correlation coefficient and Pearson's correlation coefficient between mutant allele frequencies (MAFs) assessed by NGS and dPCR revealed a positive and linear relationship between the two data sets (ρc = 0.986; 95% confidence interval [CI] = 0.975–0.991; r = 0.987; p < 0.0001, respectively), indicating an excellent concordance between both measurements. Similarly, the agreement between NGS and dPCR for the detection of the resistance mutation p.T790M was almost perfect (K = 0.81; 95% CI = 0.62–0.99), with an excellent correlation in terms of MAFs (ρc = 0.991; 95% CI = 0.981–0.992 and Pearson's r = 0.998; p < 0.0001). Importantly, cfDNA sequencing was successful using as low as 10 ng cfDNA input. Conclusions: MAFs assessed by NGS were highly correlated with MAFs assessed by dPCR, demonstrating that NGS is a robust technique for ctDNA quantification using clinical samples, thereby allowing for dynamic genomic surveillance in the era of precision medicine.
- Subjects
IRINOTECAN; NUCLEOTIDE sequencing; CIRCULATING tumor DNA; INTRACLASS correlation; NON-small-cell lung carcinoma; PEARSON correlation (Statistics); LUNG cancer
- Publication
Clinical Chemistry & Laboratory Medicine, 2020, Vol 58, Issue 2, p306
- ISSN
1434-6621
- Publication type
Article
- DOI
10.1515/cclm-2019-0745