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

Oncotarget
Hidenobu IshiiTomoaki Hoshino

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...Continue Reading

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Citations

Jul 31, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·E AlegreA Gonzalez
May 10, 2017·Molecular Diagnosis & Therapy·Susana Olmedillas-LópezDamián García-Olmo
Sep 25, 2018·Technology in Cancer Research & Treatment·Jun Lu, Baohui Han
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Jun 13, 2021·International Journal of Clinical Oncology·Ryoji KatoKazuhiko Nakagawa
Aug 28, 2021·International Journal of Molecular Sciences·Teppei HashimotoKiyoshi Matsui

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Methods Mentioned

BETA
PCR
biopsy
Fluorescence

Software Mentioned

QuantaSoft

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