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Detection of activating and acquired resistant mutation in plasma from EGFR-mutated NSCLC patients by peptide nucleic acid (PNA) clamping-assisted fluorescence melting curve analysis

Authors
 Chang Gon Kim  ;  Hyo Sup Shim  ;  Min Hee Hong  ;  Yoon Jin Cha  ;  Su Jin Heo  ;  Hyung Soon Park  ;  Jee Hung Kim  ;  Jin Gu Lee  ;  Chang Young Lee  ;  Byoung Chul Cho  ;  Hye Ryun Kim 
Citation
 Oncotarget, Vol.8(39) : 65111-65122, 2017 
Journal Title
 Oncotarget 
Issue Date
2017
Keywords
epidermal growth factor receptor mutation ; first-generation epidermal growth factor receptor-tyrosine kinase inhibitors ; liquid biopsy ; non-small cell lung cancer ; peptide nucleic acid clamping-assisted fluorescence melting curve analysis
Abstract
This study was designed to prospectively examine whether peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper™) is feasible for the detection of activating and acquired resistant epidermal growth factor receptor (EGFR) mutation in plasma. Patients with non-small cell lung cancer harboring activating EGFR mutations who were scheduled to undergo EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled between September 2011 and March 2015. A total of 102 patients with EGFR-mutated lung cancer were enrolled, 53 had available plasma samples at disease progression, and 28 underwent serial plasma sampling during EGFR-TKI treatment. EGFR-TKI-sensitizing and T790M mutations were detected in the plasma of 68.6% (70/102) at baseline and 30.2% (16/53) at disease progression, respectively. The concordance rates for matched tissue and plasma samples were 80.4% and 90.2% for E19del and L858R mutations at baseline and 56.3% for T790M mutation at disease progression. The sustained presence of plasma EGFR mutations four weeks after EGFR-TKI predicted a poor objective response rate (30.0% vs. 87.5%, P = 0.025), as well as worse progression-free survival (hazard ratio [HR], 4.381) and overall survival (HR, 5.475). Longitudinal analysis could detect T790M mutations earlier than disease progression based on imaging study (median time from appearance of T790M in plasma samples to progression at imaging scan, 103 days). In conclusion, PANAMutyper™ is reliable for detecting activating and acquired resistant EGFR mutation in plasma, and predicts responses to EGFR-TKI via longitudinal monitoring of EGFR mutation during treatment.
Files in This Item:
T201703979.pdf Download
DOI
10.18632/oncotarget.17786
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김지형(Kim, Jee Hung) ORCID logo https://orcid.org/0000-0002-9044-8540
김혜련(Kim, Hye Ryun) ORCID logo https://orcid.org/0000-0002-1842-9070
박형순(Park, Hyung Soon)
심효섭(Shim, Hyo Sup) ORCID logo https://orcid.org/0000-0002-5718-3624
이진구(Lee, Jin Gu)
이창영(Lee, Chang Young)
조병철(Cho, Byoung Chul) ORCID logo https://orcid.org/0000-0002-5562-270X
차윤진(Cha, Yoon Jin) ORCID logo https://orcid.org/0000-0002-5967-4064
허수진(Heo, Su Jin) ORCID logo https://orcid.org/0000-0002-0615-5869
홍민희(Hong, Min Hee) ORCID logo https://orcid.org/0000-0003-3490-2195
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154038
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