title: A Rapid and Sensitive Method for Detection of the T790M Mutation of EGFR in Plasma DNA.
abstract: Epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors' (EGFR-TKIs) in non-small cell lung cancer (NSCLC). The aims of this study are to develop a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients, using PointMan™ EGFR DNA Enrichment Kit which is a novel method for selective amplification of genotype specific sequences.Pairs of blood samples and tumor tissues were collected from NSCLC patients with an EGFR activating mutation and who were resistant to EGFR-TKI treatment. EGFR T790M mutation in plasma DNA were detected using the PointMan™ EGFR DNA Enrichment Kit. The concentrations of plasma DNA were determined using quantitative real-time PCR.Of the 52 patients enrolled in this study, 41 of the patients' plasma samples were collected at post EGFR-TKIs. Nineteen (46.3 %) of the 41 patients had an EGFR T790M mutation in their plasma DNA as detected using the PointMan™ EGFR DNA Enrichment Kit after disease progression to EFGR-TKI. Of 11 cases with a detected T790M mutation from tumor tissues, 10 (90.9 %) also had a detectable T790M mutation in the plasma DNA. There was no difference in the progression-free survival between patients with T790M and those without T790M.The PointMan™ proved to be a useful method for determining plasma EGFR T790M mutation status.
authors.affiliation: Respiratory Medicine, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, 920-8641, Japan. hkimura3625@staff.kanazawa-u.ac.jp.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Respiratory Medicine, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, 920-8641, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nishikawa
authors.affiliation: Respiratory Medicine, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, 920-8641, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Koba
authors.affiliation: Respiratory Medicine, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, 920-8641, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Yoneda
authors.affiliation: Respiratory Medicine, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, 920-8641, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sone
authors.affiliation: Respiratory Medicine, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa, 920-8641, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kasahara
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results
chemical_list: D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; EGFRT790M mutation; Non-small cell lung cancer