title: A comparative study of EGFR oncogenic mutations in matching tissue and plasma samples from patients with advanced non-small cell lung carcinoma.
abstract: BACKGROUND
  Plasma based EGFR mutation analysis is emerging as a viable alternative to tumour tissue genotyping for patients with non-small cell lung carcinoma (NSCLC). The purpose of the study was to determine the degree of concordance between EGFR genotypes derived from matching tissue and blood samples.
  
  
  METHODS
  EGFR activating mutations L858R, exon 19 deletions, G719A/C/S and L861Q as well as resistance mutations T790M and exon 20 insertions were co-analysed in 61 matching tissue and blood biopsies collected from NCSLC patients. Tissue and plasma genotyping was performed by amplification refractory mutation system PCR (ARMS-PCR) and circulating single molecule amplification and re-sequencing technology (cSMART), respectively.
  
  
  RESULTS
  Of the 61 paired samples, 44 (72.1%) were fully concordant, 2 (3.3%) were partially concordant and 15 (24.6%) were discordant for EGFR genotypes. The discordance was bidirectional with tissue and plasma failing to reveal the equivalent mutation in eight and nine cases, respectively. Benchmarking against ARMS-PCR tissue biopsy results as the gold standard, the sensitivity and concordance rates for plasma mutation detection by cSMART assay were 72.7% and 90.2% (L858R), 72.7% and 86.9% (exon 19 deletions) and 100% and 98.4% (T790M).
  
  
  CONCLUSIONS
  The cSMART assay was highly reliable and accurate for plasma EGFR genotyping. Based on discordance trends, tumour heterogeneity was suspected to be the major factor preventing a concordant diagnosis in matching samples.
authors.affiliation: Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, China; School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chai
authors.affiliation: Department of Molecular Pathology, The Affiliated Cancer Hospital to Zhengzhou University, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Ren
authors.affiliation: Department of Molecular Pathology, The Affiliated Cancer Hospital to Zhengzhou University, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wei
authors.affiliation: Department of Molecular Pathology, The Affiliated Cancer Hospital to Zhengzhou University, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Scientific Research and Foreign Affairs, The Affiliated Cancer Hospital of Zhengzhou University, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mai
authors.affiliation: Berry Genomics, Beijing 100015, China.
authors.forename: David S
authors.initials: DS
authors.lastname: Cram
authors.affiliation: Department of Haematology, The Affiliated Cancer Hospital of Zhengzhou University China. Electronic address: sypdoc@sina.com.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Molecular Pathology, The Affiliated Cancer Hospital to Zhengzhou University, China. Electronic address: yongjunguo@hotmail.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics*; D009154:Mutation
chemical_list: D066246:ErbB Receptors
keywords: Amplification refractory mutation system PCR; Circulating single molecule amplification and re-sequencing technology; Epithelial growth factor receptor; Non-small cell lung carcinoma; Oncogenic mutations