Investigation of EGFR mutations in non‑small cell lung cancer usually undetectable by PCR methods

Matsubara,Taisuke; Nakajima,Eiji; Namikawa,Haruka; Ono,Shotaro; Takada,Ikki; Ohira,Tatsuo; Morishita,Yukio; Miyazaki,Teruo; Furukawa,Kinya; Ikeda,Norihiko

doi:10.3892/mco.2021.2447

January-2022 Volume 16 Issue 1

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January-2022 Volume 16 Issue 1

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Article Open Access

Investigation of EGFR mutations in non‑small cell lung cancer usually undetectable by PCR methods

Authors:
- Taisuke Matsubara
- Eiji Nakajima
- Haruka Namikawa
- Shotaro Ono
- Ikki Takada
- Tatsuo Ohira
- Yukio Morishita
- Teruo Miyazaki
- Kinya Furukawa
- Norihiko Ikeda
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Affiliations: Department of Surgery, Tokyo Medical University, Tokyo 160‑0023, Japan, Department of Thoracic Surgery, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki 300‑0395, Japan, Department of Diagnostic Pathology, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki 300‑0395, Japan, Department of Joint Research Center, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki 300‑0395, Japan

Copyright: © Matsubara et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 15
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Published online on: November 21, 2021

https://doi.org/10.3892/mco.2021.2447
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Abstract

Epidermal growth factor receptor (EGFR) mutations are the most significant genomic drivers of non‑small cell lung cancer (NSCLC) and determine the efficacy of EGFR tyrosine kinase inhibitor (EGFR‑TKI) therapy. PCR methods are used clinically for the detection of EGFR mutations. The Scorpion Amplification Refractory Mutation System (Scorpion‑ARMS) and the cobas^® EGFR Mutation Test v2 (cobas v2) are widely used PCR methods. However, those PCR methods only selectively detect the common EGFR mutations. The aim of the present study was to reveal the true frequency of EGFR mutations in NSCLC by investigating EGFR mutations usually undetectable by PCR methods by using direct sequencing. A total of 70 Japanese patients who underwent lung resection for NSCLC between September 2016 and March 2019 were included in the present study. Subsequently, PCR methods and direct sequencing were performed. In total, 29 mutations were detected by cobas v2. In total, 41 patients were identified as EGFR wild‑type by cobas v2, among whom direct sequencing detected mutations in 3 patients. Subsequent Scorpion‑ARMS was performed in the 3 patients in whom direct sequencing detected mutations. In total, one exon 21 L858R + G863D compound mutation was identified as a L858R single mutation, and two other mutations were undetectable. Moreover, 1 patient who was ‘wild‑type’ on cobas v2 but ‘EGFR mutation’ on direct sequencing developed recurrence after surgery and responded to EGFR‑TKI treatment. In present study, the percentage of undetectable EGFR mutations by cobas v2 was 9.4% in 32 mutations. It was inferred that the cause of the discrepancy in the mutation type (L858R + G863D in exon 21, and L858R in exon 21) between cobas v2 and Scorpion ARMS was due to the different limit of detection between these two PCR methods. In conclusion, the findings of the present study suggested that a selective mutation detection method may decrease the opportunity of patients with NSCLC to receive EGFR‑TKI therapy. Thus, the development of a screening test to determine the EGFR status as wild‑type or mutant is required for EGFR‑TKI therapy.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Investigation of EGFR mutations in non‑small cell lung cancer usually undetectable by PCR methods

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