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Peptide Nucleic Acid Clamping Versus Direct Sequencing for the Detection of EGFR Gene Mutation in Patients with Non-small Cell Lung Cancer
Seong-Hoon Yoon, Yoo-Duk Choi, In-Jae Oh, Kyu-Sik Kim, Hayoung Choi, Jinsun Chang, Hong-Joon Shin, Cheol-Kyu Park, Young-Chul Kim
Cancer Res Treat. 2015;47(4):661-669.   Published online February 23, 2015
DOI: https://doi.org/10.4143/crt.2014.282
AbstractAbstract PDFPubReaderePub
Purpose
Direct sequencing (DS) is the standard method for detection of epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC); however, low detection sensitivity is a problem. The aim of this study is to demonstrate higher detection rate of EGFR gene mutation with peptide nucleic acid (PNA) clamping compared with DS. Materials and Methods This is a single arm, prospective study for patients with stage IIIB/IV or relapsed NSCLC. Using tumor DNA from 138 patients, both DS and PNA clamping for EGFR gene in exon 18, 19, 20, and 21 were performed. Discrepant results between the two methods were verified using Cobas and a mutant enrichment based next generation sequencing (NGS). Patients with activating mutations were treated with EGFR tyrosine kinase inhibitor (EGFR-TKI, gefitinib, or erlotinib) as first line treatment.
Results
Of 138 paired test sets, 24 (17.4%) and 45 (32.6%) cases with activating mutations were detected by DS and PNA clamping, respectively. The difference of detection rate between the two methods was 15.2% (95% confidence interval, 8.7% to 17.8%; p < 0.001). Between the two methods, 25 cases showed discrepant results (n=23, PNA+/DS–; n=2, PNA–/DS+). Mutations were confirmed by Cobas or NGS in 22 of 23 PNA+/DS– cases. The response rates to EGFR-TKI were 72.2% in the PNA+/DS+ group and 85.0% in the PNA+/DS– group. Conclusion PNA clamping showed a significantly higher detection rate of EGFR gene mutation compared with DS. Higher sensitivity of PNA clamping was not compromised by the loss of predictive power of response to EGFR-TKI.

Citations

Citations to this article as recorded by  
  • Highly Sensitive Enrichment of Low-Frequency Variants by Hairpin Competition Amplification
    Zhaocheng Liu, Rui Zhang, Xixi Jiang, Li Ji, Ping Sun, Yong Ji, Yu Zhang, Yan Ding, Koukou Li, Zhening Pu, Fengsheng Zhou, Jian Zou
    Analytical Chemistry.2023; 95(32): 12015.     CrossRef
  • Peptide Nucleic Acids: Recent Developments in the Synthesis and Backbone Modifications
    Gurpreet Singh, Vikramdeep Monga
    Bioorganic Chemistry.2023; 141: 106860.     CrossRef
  • Genetic Alterations and Risk Factors for Recurrence in Patients with Non-Small Cell Lung Cancer Who Underwent Complete Surgical Resection
    Hwa Park, Yoo Choi, Ju-Sik Yun, Sang-Yun Song, Kook-Joo Na, Joon Yoon, Chang-Seok Yoon, Hyung-Joo Oh, Young-Chul Kim, In-Jae Oh
    Cancers.2023; 15(23): 5679.     CrossRef
  • Efficacy and dose of afatinib in patients with non‐small cell lung cancer after failure of prior gefitinib or erlotinib treatment
    Hayoung Choi, Jae‐Kyeong Lee, Hyung‐Joo Oh, Min‐Seok Kim, Bo Gun Kho, Cheol Kyu Park, In‐Jae Oh, Young‐Chul Kim
    Thoracic Cancer.2021; 12(10): 1598.     CrossRef
  • Bronchial brushing cytology is comparable to bronchial biopsy for epidermal growth factor receptor mutation test in non-small cell lung cancer
    Joo-Yeon Koo, Nah-Ihm Kim, Taebum Lee, Yoo-Duk Choi
    Cytojournal.2020; 17: 16.     CrossRef
  • Potential applications of peptide nucleic acid in biomedical domain
    Kshitij RB Singh, Parikipandla Sridevi, Ravindra Pratap Singh
    Engineering Reports.2020;[Epub]     CrossRef
  • Prognostic value of quantitative measurement of EGFR mutation using peptide nucleic acid clamping in advanced EGFR mutant non‐small cell lung cancer patients
    Insu Kim, Jung Seop Eom, Eun Jung Jo, Jeongha Mok.Ki Uk, Kwangha Lee, Ki Uk Kim, Hye‐Kyung Park, Min Ki Lee, Mi‐Hyun Kim
    Thoracic Cancer.2019; 10(7): 1561.     CrossRef
  • Sensitive detection of low-abundance in-frame deletions in EGFR exon 19 using novel wild-type blockers in real-time PCR
    Xiao-Dong Ren, Ding-Yuan Liu, Hai-Qin Guo, Liu Wang, Na Zhao, Ning Su, Kun Wei, Sai Ren, Xue-Mei Qu, Xiao-Tian Dai, Qing Huang
    Scientific Reports.2019;[Epub]     CrossRef
  • Peptide Nucleic Acid Clamping and Direct Sequencing in the Detection of Oncogenic Alterations in Lung Cancer: Systematic Review and Meta-Analysis
    Jae-Uk Song, Jonghoo Lee
    Yonsei Medical Journal.2018; 59(2): 211.     CrossRef
  • Comparative analysis of Adam33 mutations in murine lung cancer cell lines by droplet digital PCR, real-time PCR and Insight Onco™ NGS
    Soo-Jin Kim, Eunhee Kim, Kyung-Taek Rim
    Molecular & Cellular Toxicology.2018; 14(2): 221.     CrossRef
  • Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer
    Tae‐Ok Kim, In‐Jae Oh, Bo Gun Kho, Ha Young Park, Jin Sun Chang, Cheol‐Kyu Park, Hong‐Joon Shin, Jung‐Hwan Lim, Yong‐Soo Kwon, Yu‐Il Kim, Sung‐Chul Lim, Young‐Chul Kim, Yoo‐Duk Choi
    Thoracic Cancer.2018; 9(7): 856.     CrossRef
  • Clinical Activity of Pan-HER Inhibitors Against HER2-Mutant Lung Adenocarcinoma
    In-Jae Oh, Jae Young Hur, Cheol-Kyu Park, Young-Chul Kim, Seung Joon Kim, Min Ki Lee, Hee Joung Kim, Kye Young Lee, Jae Cheol Lee, Chang-Min Choi
    Clinical Lung Cancer.2018; 19(5): e775.     CrossRef
  • Genetic Biomarkers and Their Applications to Prevent Occupational Diseases: A Literature Review
    Kyung-Taek Rim
    Toxicology and Environmental Health Sciences.2018; 10(3): 147.     CrossRef
  • Molecular masquerading of rare EGFR L858M/L861R mutations as common L858R/L861Q mutations by PNA clamping assay
    Ji Hyung Hong, Seung-Hyun Jung, Min Sung Kim, Sug Hyung Lee, Yeun-Jun Chung
    Pathology.2017; 49(4): 453.     CrossRef
  • Mutations of the Epidermal Growth Factor Receptor Gene in Triple-Negative Breast Cancer
    Aeri Kim, Min Hye Jang, Soo Jung Lee, Young Kyung Bae
    Journal of Breast Cancer.2017; 20(2): 150.     CrossRef
  • Peptide nucleic acids: Advanced tools for biomedical applications
    Anjali Gupta, Anuradha Mishra, Nidhi Puri
    Journal of Biotechnology.2017; 259: 148.     CrossRef
  • Non-invasive quantification of cell-free DNA mutations in plasma during lung tumor progression in mice
    Soo-Jin Kim, Eunhee Kim, Kyung-Taek Rim
    Cancer Biomarkers.2017; 20(4): 477.     CrossRef
  • Peptide Nucleic Acid-Based Biosensors for Cancer Diagnosis
    Roberta D’Agata, Maria Giuffrida, Giuseppe Spoto
    Molecules.2017; 22(11): 1951.     CrossRef
  • Generation of lung cancer cell lines harboring EGFR T790M mutation by CRISPR/Cas9-mediated genome editing
    Mi-Young Park, Min Hee Jung, Eun Young Eo, Seokjoong Kim, Sang Hoon Lee, Yeon Joo Lee, Jong Sun Park, Young Jae Cho, Jin Haeng Chung, Cheol Hyeon Kim, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee
    Oncotarget.2017; 8(22): 36331.     CrossRef
  • Application of Peptide Nucleic Acid-based Assays Toward Detection of Somatic Mosaicism
    Christopher S Hong, Chunzhang Yang, Zhengping Zhuang
    Molecular Therapy - Nucleic Acids.2016; 5: e314.     CrossRef
  • Quantification of epidermal growth factor receptor (EGFR) mutation may be a predictor of EGFR‐tyrosine kinase inhibitor treatment response
    Ha Young Park, Hyung Joo Oh, Ki‐Hyun Kim, Tae‐Ok Kim, Cheol‐Kyu Park, Hong‐Jun Shin, Jung‐Hwan Lim, Yong‐Soo Kwon, In‐Jae Oh, Yu‐Il Kim, Sung‐Chul Lim, Young‐Chul Kim, Yoo‐Duk Choi
    Thoracic Cancer.2016; 7(6): 639.     CrossRef
  • Association between GWAS-identified lung adenocarcinoma susceptibility loci andEGFRmutations in never-smoking Asian women, and comparison with findings from Western populations
    Wei Jie Seow, Keitaro Matsuo, Chao Agnes Hsiung, Kouya Shiraishi, Minsun Song, Hee Nam Kim, Maria Pik Wong, Yun-Chul Hong, H. Dean Hosgood, Zhaoming Wang, I-Shou Chang, Jiu-Cun Wang, Nilanjan Chatterjee, Margaret Tucker, Hu Wei, Tetsuya Mitsudomi, Wei Zhe
    Human Molecular Genetics.2016; : ddw414.     CrossRef
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  • 20 Web of Science
  • 22 Crossref
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Results of Curative Radiation Therapy with or without Chemotherapy for Stage III Unresectable Non-Small Cell Lung Cancer
Sung-Ja Ahn, Young-Chul Kim, Kyu-Sik Kim, Kyung-Ok Park, Woong-Ki Chung, Taek-Keun Nam, Byung-Sik Nah, Ju-Young Song, Mi-Sun Yoon
Cancer Res Treat. 2005;37(5):268-272.   Published online October 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.5.268
AbstractAbstract PDFPubReaderePub
Purpose

We retrospectively analyzed the patients who received curative radiotherapy for unresectable stage III NSCLC to investigate the impact of chemotherapy.

Materials and Methods

From 1998 to 2001, the records of 224 patients who completed curative radiotherapy for NSCLC were reviewed. There were 210 males and 14 females, and their median age was 64 years (range 38~83). 54 patients had stage IIIA disease and 170 patients had stage IIIB disease. Conventional radiotherapy was given and the radiation dose ranged from 50~70 Gy with a median of 60 Gy, and chemotherapy was combined for 116 patients (52%).

Results

The median survival, the 2-year, and 5-year actuarial survival rates of all 224 patients were 15 months, 30%, and 7%, respectively. The median survival of the patients with stage IIIA and IIIB disease were 21 months and 13 months, respectively (p=0.14). The median survival of patients who received chemoradiation was 18 months compared to 14 months for the patients who received RT alone (p=0.02). Among the chemoradiation group of patients, the median survival time of the patients who received 1 to 3 cycles of chemotherapy was 16 months and that for the patients who received more than 3 cycles was 22 months (p=0.07). We evaluated the effects of the timing of chemoradiation in 57 patients who received more than 3 cycles of chemotherapy. The median survival of the patients with the concurrent sequence was 25 months and that for the patients with the sequential chemotherapy was 19 months (p=0.81).

Conclusions

For advanced stage III non-small cell lung cancer patients who completed the curative radiotherapy, the addition of chemotherapy improved the survival compared to the patients who received radiotherapy alone.

Citations

Citations to this article as recorded by  
  • Treatment for Non-Small-Cell Lung Cancer and Circulating Tumor Cells
    Joel Mason, Benjamin Blyth, Michael P MacManus, Olga A Martin
    Lung Cancer Management.2017; 6(4): 129.     CrossRef
  • Clinical Responses and Prognostic Indicators of Concurrent Chemoradiation for Non-small Cell Lung Cancer
    Dong-Soo Lee, Yeon-Sil Kim, Jin-Hyoung Kang, Sang-Nam Lee, Young-Kyoun Kim, Myung-Im Ahn, Dae-Hee Han, Ie-Ryung Yoo, Young-Pil Wang, Jae-Gil Park, Sei-Chul Yoon, Hong-Seok Jang, Byung-Oak Choi
    Cancer Research and Treatment.2011; 43(1): 32.     CrossRef
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  • 66 Download
  • 2 Crossref
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