title: Predictive efficacy of low burden EGFR mutation detected by next-generation sequencing on response to EGFR tyrosine kinase inhibitors in non-small-cell lung carcinoma.
abstract: Direct sequencing remains the most widely used method for the detection of epidermal growth factor receptor (EGFR) mutations in lung cancer; however, its relatively low sensitivity limits its clinical use. The objective of this study was to investigate the sensitivity of detecting an epidermal growth factor receptor (EGFR) mutation from peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp and Ion Torrent Personal Genome Machine (PGM) techniques compared to that by direct sequencing. Furthermore, the predictive efficacy of EGFR mutations detected by PNA-LNA PCR clamp was evaluated. EGFR mutational status was assessed by direct sequencing, PNA-LNA PCR clamp, and Ion Torrent PGM in 57 patients with non-small cell lung cancer (NSCLC). We evaluated the predictive efficacy of PNA-LNA PCR clamp on the EGFR-TKI treatment in 36 patients with advanced NSCLC retrospectively. Compared to direct sequencing (16/57, 28.1%), PNA-LNA PCR clamp (27/57, 47.4%) and Ion Torrent PGM (26/57, 45.6%) detected more EGFR mutations. EGFR mutant patients had significantly longer progressive free survival (14.31 vs. 21.61 months, P = 0.003) than that of EGFR wild patients when tested with PNA-LNA PCR clamp. However, no difference in response rate to EGFR TKIs (75.0% vs. 82.4%, P = 0.195) or overall survival (34.39 vs. 44.10 months, P = 0.422) was observed between the EGFR mutations by direct sequencing or PNA-LNA PCR clamp. Our results demonstrate firstly that patients with EGFR mutations were detected more frequently by PNA-LNA PCR clamp and Ion Torrent PGM than those by direct sequencing. EGFR mutations detected by PNA-LNA PCR clamp may be as a predicative factor for EGFR TKI response in patients with NSCLC.
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Korea University, Seoul, Korea.
authors.forename: Jae Sook
authors.initials: JS
authors.lastname: Sung
authors.affiliation: Macroge Inc., Seoul, Korea.
authors.forename: Song-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Macroge Inc., Seoul, Korea.
authors.forename: Nak-Jung
authors.initials: NJ
authors.lastname: Kwon
authors.affiliation: Cancer Research Institute, Korea University, Seoul, Korea.
authors.forename: LiHua
authors.initials: L
authors.lastname: Jin
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Kyong Hwa
authors.initials: KH
authors.lastname: Park
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Shin
authors.affiliation: Department of Pathology, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Han Kyeom
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Seoul Saint Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jin-Hyoung
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Laboratory of Medical Oncology, Research Institutes of Medical Science, The Catholic University of Korea, Korea.
authors.forename: Jeong-Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Korea.
authors.forename: HyoungKyu
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Division of Pulmonology, Department of Internal Medicine, Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Korea.
authors.forename: Chan Kwon
authors.initials: CK
authors.lastname: Park
authors.affiliation: Macroge Inc., Seoul, Korea.
authors.forename: Kap-Seok
authors.initials: KS
authors.lastname: Yang
authors.affiliation: Macroge Inc., Seoul, Korea ; Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Korea ; Department of Biochemistry, Seoul National University College of Medicine, Seoul, Korea ; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea ; Cancer Research Institute, Korea University, Seoul, Korea.
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D023281:Genomics / Q000295:instrumentation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D009841:Oligonucleotides; D020135:Peptide Nucleic Acids; D016133:Polymerase Chain Reaction; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D009841:Oligonucleotides; D020135:Peptide Nucleic Acids; D047428:Protein Kinase Inhibitors; C477371:locked nucleic acid; D066246:ErbB Receptors