Multiplex picoliter-droplet digital PCR for quantitative assessment of EGFR mutations in circulating cell-free DNA derived from advanced non-small cell lung cancer patients
| Autor: | Meilin Zhang, Baisheng Pan, Wei Guo, Haiying Ji, Jiong Wu, Beili Wang, Fei Huang, Ying Zhao, Shenchao Wu, Chunyan Zhang, Qian Yu, Xin Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Lung Neoplasms Biology medicine.disease_cause Biochemistry 03 medical and health sciences T790M 0302 clinical medicine Carcinoma Non-Small-Cell Lung Multiplex polymerase chain reaction Genetics medicine Humans Digital polymerase chain reaction Multiplex Liquid biopsy Lung cancer Protein Kinase Inhibitors Molecular Biology non-small cell lung cancer Alleles Aged picoliter-droplet digital PCR liquid biopsy Cancer Articles Middle Aged circulating cell-free DNA medicine.disease Molecular biology respiratory tract diseases ErbB Receptors 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Mutation Cancer research Molecular Medicine Female epidermal growth factor receptor Carcinogenesis Cell-Free Nucleic Acids Multiplex Polymerase Chain Reaction |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | To explore the possible diagnostic value of liquid biopsy, two multiplex panels using picoliter-droplet digital polymerase chain reaction (ddPCR) were established to quantitatively assess the epidermal growth factor receptor (EGFR) mutations in cell‑free DNA (cfDNA) extracted from the plasma of advanced non‑small cell lung cancer (NSCLC) patients. Plasma samples derived from 22 patients with stage IIIB/IV NSCLC harboring EGFR mutations in matched tumor tissues confirmed by amplification refractory mutation system (ARMS) analysis were subjected to two multiplex ddPCR panels to assess the abundance of tyrosine kinase inhibitor (TKI) ‑sensitive (19DEL, L858R) and TKI‑resistant (T790 M) mutations. Fluctuations in EGFR mutant abundance were monitored by either of the multiplex ddPCR panels for three patients undergoing EGFR‑TKI treatment, with serial plasma sample collections over 2 months. The multiplex ddPCR panels applied to plasma cfDNA from advanced NSCLC patients achieved a total concordance rate of 80% with the EGFR mutation profiles obtained by ARMS from matched biopsy tumor specimens (90% for 19DEL, 95% for L858R, 95% for T790M, respectively) and revealed additional mutant alleles in two subjects. The respective sensitivity and specificity were 90.9 and 88.9% for 19DEL, 87.5 and 100% for L858R, 100 and 93.8% for T790M. The fluctuations of EGFR mutant abundance in serial plasma cfDNA were in accordance with the changes in tumor size as assessed by imaging scans. The authors demonstrated the utility of multiplex ddPCR panels with ultra‑sensitivity for quantitative analysis of EGFR mutations in plasma cfDNA and obtained promising usefulness in EGFR‑TKI decision‑making for advanced NSCLC patients. |
| Databáze: | OpenAIRE |
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