Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison
Third-generation tyrosine kinase inhibitors (TKIs) were developed to overcome T790M-mediated resistance to earlier generations of epidermal growth factor receptor (EGFR)-targeted TKIs. We compared four well-established and one in-house method for the analysis of the EGFR T790M mutation in plasma cel...
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| Format: | Article |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.00631/full |
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| author | Yi-Lin Chen Yi-Lin Chen Yi-Lin Chen Chien-Chung Lin Shu-Ching Yang Shu-Ching Yang Wan-Li Chen Wan-Li Chen Jian-Rong Chen Jian-Rong Chen Yi-Hsin Hou Yi-Hsin Hou Cheng-Chan Lu Cheng-Chan Lu Cheng-Chan Lu Nan-Haw Chow Nan-Haw Chow Nan-Haw Chow Wu-Chou Su Wu-Chou Su Chung-Liang Ho Chung-Liang Ho Chung-Liang Ho |
| author_facet | Yi-Lin Chen Yi-Lin Chen Yi-Lin Chen Chien-Chung Lin Shu-Ching Yang Shu-Ching Yang Wan-Li Chen Wan-Li Chen Jian-Rong Chen Jian-Rong Chen Yi-Hsin Hou Yi-Hsin Hou Cheng-Chan Lu Cheng-Chan Lu Cheng-Chan Lu Nan-Haw Chow Nan-Haw Chow Nan-Haw Chow Wu-Chou Su Wu-Chou Su Chung-Liang Ho Chung-Liang Ho Chung-Liang Ho |
| author_sort | Yi-Lin Chen |
| collection | DOAJ |
| description | Third-generation tyrosine kinase inhibitors (TKIs) were developed to overcome T790M-mediated resistance to earlier generations of epidermal growth factor receptor (EGFR)-targeted TKIs. We compared four well-established and one in-house method for the analysis of the EGFR T790M mutation in plasma cell-free DNA (cfDNA), in hope to find a better way to select non-small cell lung cancer (NSCLC) patients appropriate for 3rd-generation TKI therapy. For sensitivity levels of each method, plasmid DNA with EGFR T790M mutations was serially diluted with cfDNA from healthy controls with wild type EGFR. The clinical performance was analyzed in a clinical cohort of EGFR mutation-positive NSCLC patients with acquired EGFR TKI resistance (n = 40). All methods except the therascreen kit (Qiagen) had a sensitivity level of 10 copies of T790M plasmid DNA in the spiked specimen. The detection rates of the EGFR T790M mutation in plasma cfDNA from the clinical cohort were 42.5, 35, 32.5, 22.5, and 17.5% for the in-house ARMS method, Bio-Rad droplet digital PCR, PANAMutyper, Therascreen EGFR Plasma RGQ PCR Kit and Cobas EGFR Mutation kit (with suboptimal template amounts), respectively. Osimertinib was given to 17 of 20 patients with EGFR T790M mutations. The best treatment responses, based on the RECIST criteria, included 6 partial responses (PR) and 7 stable diseases (SD). The PANAMutyper and the Bio-Rad droplet digital PCR were comparable, the Cobas EGFR Mutation kit required significantly more template for testing. The best combination would be the in-house ARMS method plus the PANAMutyper or Bio-Rad droplet digital PCR, which would have a detection rate of 50% (20/40) and a disease control rate of 76% (13/17). |
| first_indexed | 2024-12-19T08:19:17Z |
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| id | doaj.art-4d445a92355640e0a8207cd5b957c13c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T08:19:17Z |
| publishDate | 2019-07-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-4d445a92355640e0a8207cd5b957c13c2022-12-21T20:29:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-07-01910.3389/fonc.2019.00631461857Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A ComparisonYi-Lin Chen0Yi-Lin Chen1Yi-Lin Chen2Chien-Chung Lin3Shu-Ching Yang4Shu-Ching Yang5Wan-Li Chen6Wan-Li Chen7Jian-Rong Chen8Jian-Rong Chen9Yi-Hsin Hou10Yi-Hsin Hou11Cheng-Chan Lu12Cheng-Chan Lu13Cheng-Chan Lu14Nan-Haw Chow15Nan-Haw Chow16Nan-Haw Chow17Wu-Chou Su18Wu-Chou Su19Chung-Liang Ho20Chung-Liang Ho21Chung-Liang Ho22Molecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanAssociation of Medical Technologists, Tainan, TaiwanDepartment of Internal Medicine, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanCollege of Medicine, Institute of Molecular Medicine, National Cheng Kung University, Tainan, TaiwanMolecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanCollege of Medicine, Institute of Molecular Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Internal Medicine, National Cheng Kung University Hospital, Tainan, TaiwanCollege of Medicine, Institute of Molecular Medicine, National Cheng Kung University, Tainan, TaiwanMolecular Diagnosis Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, TaiwanMolecular Medicine Core Laboratory, Research Center of Clinical Medicine, National Cheng Kung University Hospital, Tainan, TaiwanCollege of Medicine, Institute of Molecular Medicine, National Cheng Kung University, Tainan, TaiwanThird-generation tyrosine kinase inhibitors (TKIs) were developed to overcome T790M-mediated resistance to earlier generations of epidermal growth factor receptor (EGFR)-targeted TKIs. We compared four well-established and one in-house method for the analysis of the EGFR T790M mutation in plasma cell-free DNA (cfDNA), in hope to find a better way to select non-small cell lung cancer (NSCLC) patients appropriate for 3rd-generation TKI therapy. For sensitivity levels of each method, plasmid DNA with EGFR T790M mutations was serially diluted with cfDNA from healthy controls with wild type EGFR. The clinical performance was analyzed in a clinical cohort of EGFR mutation-positive NSCLC patients with acquired EGFR TKI resistance (n = 40). All methods except the therascreen kit (Qiagen) had a sensitivity level of 10 copies of T790M plasmid DNA in the spiked specimen. The detection rates of the EGFR T790M mutation in plasma cfDNA from the clinical cohort were 42.5, 35, 32.5, 22.5, and 17.5% for the in-house ARMS method, Bio-Rad droplet digital PCR, PANAMutyper, Therascreen EGFR Plasma RGQ PCR Kit and Cobas EGFR Mutation kit (with suboptimal template amounts), respectively. Osimertinib was given to 17 of 20 patients with EGFR T790M mutations. The best treatment responses, based on the RECIST criteria, included 6 partial responses (PR) and 7 stable diseases (SD). The PANAMutyper and the Bio-Rad droplet digital PCR were comparable, the Cobas EGFR Mutation kit required significantly more template for testing. The best combination would be the in-house ARMS method plus the PANAMutyper or Bio-Rad droplet digital PCR, which would have a detection rate of 50% (20/40) and a disease control rate of 76% (13/17).https://www.frontiersin.org/article/10.3389/fonc.2019.00631/fullepidermal growth factor receptorcell-free DNAnon-small cell lung canceramplification refractory mutation systemcapillary electrophoresistyrosine kinase inhibitors |
| spellingShingle | Yi-Lin Chen Yi-Lin Chen Yi-Lin Chen Chien-Chung Lin Shu-Ching Yang Shu-Ching Yang Wan-Li Chen Wan-Li Chen Jian-Rong Chen Jian-Rong Chen Yi-Hsin Hou Yi-Hsin Hou Cheng-Chan Lu Cheng-Chan Lu Cheng-Chan Lu Nan-Haw Chow Nan-Haw Chow Nan-Haw Chow Wu-Chou Su Wu-Chou Su Chung-Liang Ho Chung-Liang Ho Chung-Liang Ho Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison Frontiers in Oncology epidermal growth factor receptor cell-free DNA non-small cell lung cancer amplification refractory mutation system capillary electrophoresis tyrosine kinase inhibitors |
| title | Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison |
| title_full | Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison |
| title_fullStr | Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison |
| title_full_unstemmed | Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison |
| title_short | Five Technologies for Detecting the EGFR T790M Mutation in the Circulating Cell-Free DNA of Patients With Non-small Cell Lung Cancer: A Comparison |
| title_sort | five technologies for detecting the egfr t790m mutation in the circulating cell free dna of patients with non small cell lung cancer a comparison |
| topic | epidermal growth factor receptor cell-free DNA non-small cell lung cancer amplification refractory mutation system capillary electrophoresis tyrosine kinase inhibitors |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.00631/full |
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