Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC

Correlation with paired tumor samples

Hidenobu Ishii, Koichi Azuma, Kazuko Sakai, Akihiko Kawahara, Kazuhiko Yamada, Takaaki Tokito, Isamu Okamoto, Kazuto Nishio, Tomoaki Hoshino

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

As the development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has become an issue of concern, identification of the mechanisms responsible has become an urgent priority. However, for research purposes, it is not easy to obtain tumor samples from patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) that has relapsed after treatment with EGFR-TKIs. Here, using digital PCR assay as an alternative and noninvasive method, we examined plasma and tumor samples from patients with relapsed NSCLC to establish the inter-relationships existing among T790M mutation, activating EGFR mutations, HER2 amplification, and MET amplification. Paired samples of tumor and blood were obtained from a total of 18 patients with NSCLC after they had developed resistance to EGFR-TKI treatment, and the mechanisms of resistance were analyzed by digital PCR. Digital PCR analysis of T790M mutation in plasma had a sensitivity of 81.8% and specificity of 85.7%, the overall concordance between plasma and tissue samples being 83.3%. MET gene copy number gain in tumor DNA was observed by digital PCR in three patients, of whom one exhibited positivity for MET amplification by FISH, whereas no patient demonstrated MET and HER2 copy number gain in plasma DNA. Digital PCR analysis of plasma is feasible and accurate for detection of T790M mutation in NSCLC that becomes resistant to treatment with EGFR-TKIs.

Original languageEnglish
Pages (from-to)30850-30858
Number of pages9
JournalOncotarget
Volume6
Issue number31
DOIs
Publication statusPublished - Jan 1 2015

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Plasma Cells
Epidermal Growth Factor Receptor
Drug Resistance
Non-Small Cell Lung Carcinoma
Polymerase Chain Reaction
Protein-Tyrosine Kinases
DNA
Mutation
Neoplasms
Gene Dosage
Therapeutics
Sensitivity and Specificity
Research

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC : Correlation with paired tumor samples. / Ishii, Hidenobu; Azuma, Koichi; Sakai, Kazuko; Kawahara, Akihiko; Yamada, Kazuhiko; Tokito, Takaaki; Okamoto, Isamu; Nishio, Kazuto; Hoshino, Tomoaki.

In: Oncotarget, Vol. 6, No. 31, 01.01.2015, p. 30850-30858.

Research output: Contribution to journalArticle

Ishii, Hidenobu ; Azuma, Koichi ; Sakai, Kazuko ; Kawahara, Akihiko ; Yamada, Kazuhiko ; Tokito, Takaaki ; Okamoto, Isamu ; Nishio, Kazuto ; Hoshino, Tomoaki. / Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance mechanisms in EGFR mutant NSCLC : Correlation with paired tumor samples. In: Oncotarget. 2015 ; Vol. 6, No. 31. pp. 30850-30858.
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