Identification of genomic alterations acquired during treatment with EGFR-TKIs in non-small cell lung cancer

Naoki Kubo, Taishi Harada, Yoshimasa Shiraishi, Kaname Nosaki, Noriaki Nakagaki, Masafumi Takeshita, Hiroshi Ouchi, Eiji Iwama, Kentaro Tanaka, Isamu Okamoto, Hiroyuki Sasaki, Yoichi Nakanishi

Research output: Contribution to journalArticle

Abstract

Background/Aim: Patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) eventually develop resistance to these drugs. Although various mechanisms of such resistance have been identified, the mechanism in many cases remains unknown. Materials and Methods: Whole-exome sequencing was performed for tumor tissue from 15 patients with NSCLC who developed EGFR-TKI resistance. Tumor specimens obtained before EGFR-TKI treatment were also analyzed for four patients and normal white blood cell samples for six patients in order to detect genomic alterations that occurred during treatment. Results: The mutational signature and mutational load acquired during EGFR-TKI treatment varied among patients, with common EGFR-TKI resistance mechanisms including the T790M secondary mutation of EGFR and MET amplification being acquired together with many other genomic alterations. Our results provide insight into the mutational landscape acquired during the development of EGFR-TKI resistance in NSCLC.

Original languageEnglish
Pages (from-to)671-677
Number of pages7
JournalAnticancer research
Volume39
Issue number2
DOIs
Publication statusPublished - Feb 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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