Title |
Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value
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Published in |
Tumor Biology, July 2016
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DOI | 10.1007/s13277-016-5282-9 |
Pubmed ID | |
Authors |
E. Alegre, J. P. Fusco, P. Restituto, D. Salas-Benito, M. E. Rodríguez-Ruiz, M. P. Andueza, M. J. Pajares, A. Patiño-García, R. Pio, M. D. Lozano, A. Gúrpide, J. M. Lopez-Picazo, I. Gil-Bazo, J. L. Perez-Gracia, A. Gonzalez |
Abstract |
Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of EGFR analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and EGFR-activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type EGFR, L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating EGFR copy levels than stage I (3523 vs. 1003 copies/mL; p < 0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total EGFR copy levels above the median presented decreased overall survival (OS) (341 vs. 870 days, p < 0.05) and progression-free survival (PFS) (238 vs. 783 days; p < 0.05) compared with those with total EGFR copy levels below the median. Patients with baseline concentrations of activating mutations above the median (94 copies/mL) had lower OS (317 vs. 805 days; p < 0.05) and PFS (195 vs. 724 days; p < 0.05). During follow-up, T790M resistance mutation was detected in 53 % of patients. Total and mutated EGFR analysis in cfDNA seems a relevant tool to characterize the molecular profile and prognosis of NSCLC patients harboring EGFR mutations. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Sweden | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 53 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 9 | 17% |
Student > Master | 7 | 13% |
Student > Ph. D. Student | 5 | 9% |
Professor | 5 | 9% |
Student > Bachelor | 4 | 8% |
Other | 15 | 28% |
Unknown | 8 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 17 | 32% |
Biochemistry, Genetics and Molecular Biology | 8 | 15% |
Agricultural and Biological Sciences | 5 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
Nursing and Health Professions | 2 | 4% |
Other | 5 | 9% |
Unknown | 13 | 25% |