Comparison of three methods for detecting epidermal growth factor receptor mutations in plasma DNA samples of Chinese patients with advanced non-small cell lung cancer.
- Author:
Ling QIN
1
;
Wei ZHONG
;
Li ZHANG
;
Long-yun LI
;
Meng-zhao WANG
Author Information
- Publication Type:Journal Article
- MeSH: Asian Continental Ancestry Group; genetics; Carcinoma, Non-Small-Cell Lung; genetics; Chromatography, High Pressure Liquid; DNA Mutational Analysis; methods; Exons; genetics; Female; Humans; Male; Middle Aged; Mutation; Polymerase Chain Reaction; Receptor, Epidermal Growth Factor; genetics; Reproducibility of Results; Sequence Analysis, DNA
- From: Chinese Medical Journal 2011;124(6):887-891
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDEpidermal growth factor receptor (EGFR) mutations can predict tumor response to tyrosine kinase inhibitors (TKIs). Detecting EGFR mutations in plasma DNA samples in patients with advanced non-small cell lung cancer is challenging and promising. We compared three methods for detecting plasma EGFR mutations, including direct DNA sequencing, denaturing high-performance liquid chromatography (DHPLC) and Scorpions Amplification Refractory Mutation System (Scorpions ARMS).
METHODSPlasma DNA samples from 73 patients with stage IIIB to IV adenocarcinoma were analyzed for EGFR mutations in exons 19 (deletion mutation) and 21 (L858R mutation) using direct DNA sequencing, DHPLC and Scorpions ARMS. Sensitivities of the three methods were compared and the relationship between EGFR mutations and patients' survival was analyzed.
RESULTSIn 73 patients, we detected EGFR mutations in 5 samples (6.9%) by direct DNA sequencing, in 22 samples (30.1%) by DHPLC, and in 28 samples (38.4%) by Scorpions ARMS. EGFR mutations were found in 13 samples in exon 19 and in 9 samples in exon 21 by DHPLC, while we found mutations in 15 samples in exon 19 and in 13 samples in exon 21 by Scorpions ARMS. Among the 73 patients, there was 90.4% concordance between DHPLC and Scorpions ARMS (66/73, κ = 0.79, P = 0.07). Of the 73 patients, 46 patients were treated with gefitinib, including 18 patients with mutations and 28 patients without mutations as determined by Scorpions ARMS. The 18 patients with mutations had a significantly longer progression-free survival (PFS) time (median PFS was 21.0 months) than the 28 patients without mutations (median PFS was 7.0 months) (P = 0.022).
CONCLUSIONSAmong the three methods for detecting EGFR mutations in plasma DNA samples of patients with advanced lung adenocarcinoma, direct gene sequencing had the lowest sensitivity, while Scorpion ARMS showed the highest mutation detecting capability. DHPLC is slightly less sensitive than Scorpion ARMS. EGFR mutations in exons 19 (deletion mutation) and 21 (L858R mutation) predict a longer PFS.
