Non-invasive detection of EGFR deletion at exon 19 in non-small cell lung cancer by real time diagnostic

Clin Lab. 2014;60(9):1517-26. doi: 10.7754/clin.lab.2014.140106.

Abstract

Background: The non-invasive identification of epidermal growth factor receptor (EGFR) mutations is important for the institution of individualized therapy of non-small cell lung cancer (NSCLC). In this study, the feasibility of screening for EGFR exon 19 E746_A750del mutations in circulating DNA from plasma was assessed.

Methods: Mutant-specific primers with a Taqman probe (MST-PCR) were designed. The ability of this method to accurately detect decreasing concentrations of E746_A750del mutant within a wild type DNA background that mimics the situation of a plasma sample from patients with acquired mutations is verified. To verify the clinical applicability of this method, 55 plasma samples from NSCLC patients were tested, and the sensitivity of MST-PCR was compared to that of direct sequencing.

Results: The results showed that MST-PCR could detect 10 to 50 copies/microL of E746_A750del, representing 0.1% of the wild type EGFR allelic population. Among the 55 cases of NSCLC, 10 cases of E746_A750del were detected by MST-PCR, while only 1 case was revealed by direct sequencing.

Conclusions: These findings demonstrate that MST-PCR provides superior sensitivity for the detection of the E746_A750del mutation, suggesting its potential application in the noninvasive detection of E746_A750del mutations in plasma samples from NSCLC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis
  • ErbB Receptors / blood
  • ErbB Receptors / genetics*
  • Exons*
  • Feasibility Studies
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Phenotype
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Prognosis
  • Sequence Deletion*

Substances

  • Biomarkers, Tumor
  • EGFR protein, human
  • ErbB Receptors