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Oncol Lett. 2016 Apr;11(4):2573-2579. Epub 2016 Feb 23.

A sensitive and practical method to detect the T790M mutation in the epidermal growth factor receptor.

Author information

1
Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China.
2
Beijing BGI-GBI Biotech Co., Ltd., Beijing 101300, P.R. China.
3
Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.
4
Beijing BGI-GBI Biotech Co., Ltd., Beijing 101300, P.R. China; Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, P.R. China.

Abstract

The current study aimed to develop a method to rapidly, sensitively and practically screen for the epidermal growth factor receptor (EGFR) T790M mutation. This method combines an allele-specific competitive blocker (ACB) with a TaqMan quantitative polymerase chain reaction (PCR) amplification refractory mutation system (ARMS) in a one-step reaction. Using a mimic of a human genomic DNA panel containing serially diluted mutant alleles, the performance efficacy of this method was assessed. Using this method, the EGFR T790M mutation was detected in tyrosine kinase inhibitor (TKI)-naïve samples obtained from 27 non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. The association between de novo T790M mutations and the clinical benefit of EGFR-TKI treatment was also analysed. The sensitivity of this method was as low as 0.01%. In the samples from the 27 NSCLC patients, this method identified 6 mutant patients (22.2%), which was higher than the detection rate with scorpion ARMS (0.0%). No clinical variables were associated with the occurrence of a de novo T790M mutation. The median progression-free survival time in the TKI-naïve patients with a T790M mutation was shorter that that of patients without the mutation, but the difference was not significant (3.2 vs. 19.5 months, respectively; P=0.256). The median overall survival time in the groups with or without T790M mutation also did not significantly differ (10 vs. 20 months, respectively; P=0.689). Overall, the ACB-ARMS PCR method could be useful for detecting the EGFR T790M mutation in clinical samples that contain only a small number of mutant alleles. The clinical significance of a de novo T790M mutation should be further investigated.

KEYWORDS:

T790M mutation; allele-specific competitive blocker-amplification refractory mutation system TaqMan quantitative polymerase chain reaction; epidermal growth factor receptor; non-small cell lung cancer

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