title: Highly sensitive and noninvasive detection of epidermal growth factor receptor T790M mutation in non-small cell lung cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) T790M mutation is associated with EGFR tyrosine kinase inhibitors resistance in non-small cell lung cancer (NSCLC). However, the tissue availability and technical feasibility limits the genotyping of EGFR T790M mutation in the clinical setting. The current study is, therefore, designed to develop a blood-based approach to detect the EGFR T790M mutation in advanced NSCLC patients.
  
  
  METHODS
  The detection of EGFR T790M mutation is based on the principle of mutant-enriched PCR. We assessed the basic performance efficiency of this method, and confirmed its clinical applicability. EGFR T790M mutation in the plasma samples obtained from 33 patients with gefitinib-resistant NSCLC was analyzed by the both mutant-enriched PCR and direct sequencing.
  
  
  RESULTS
  The sensitivity of this method for the detection of EGFR T790M mutation was as low as 0.1%. In the 33 subjects whose samples were analyzed, the mutant-enriched PCR indentified more EGFR T790M mutation than direct sequencing (36.4% vs. 6.1%, P=0.005), and the EGFR T790M mutation was more frequent in patients with EGFR activating mutations than those without EGFR activating mutations (62.5% vs. 11.8%, P=0.004). Patients with EGFR T790M mutation have a better prior efficacy of gefitinib compared to those without EGFR T790M mutation due to the occurrence of the EGFR activating mutations.
  
  
  CONCLUSIONS
  The blood-based mutant-enriched PCR is an ideal noninvasive monitoring system for detecting EGFR T790M mutation for clinical application.
authors.affiliation: Department of Respiratory, the Affiliated Shenzhen Bao'an Hospital of Southern Medical University, Shenzhen, Guangdong, 518101, China. Electronic address: hecheen@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: He
authors.forename: Lixia
authors.initials: L
authors.lastname: Zheng
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Yuanguang
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000097:blood* / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFR; Epidermal growth factor receptor; Mutant-enriched PCR; NSCLC; Non-small cell lung cancer; Plasma; RFLP; Restriction fragment length polymorphism; Scorpion amplified refractory mutation system; Scorpions ARMS; Sequencing; T790M mutation; TKIs; Tyrosine kinase inhibitors