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

研究成果: ジャーナルへの寄稿記事

抄録

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.

元の言語英語
ページ(範囲)671-677
ページ数7
ジャーナルAnticancer research
39
発行部数2
DOI
出版物ステータス出版済み - 2 1 2019

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Therapeutics
Exome
Drug Resistance
Neoplasms
Leukocytes
Mutation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Kubo, N., Harada, T., Shiraishi, Y., Nosaki, K., Nakagaki, N., Takeshita, M., ... Nakanishi, Y. (2019). Identification of genomic alterations acquired during treatment with EGFR-TKIs in non-small cell lung cancer. Anticancer research, 39(2), 671-677. https://doi.org/10.21873/anticanres.13162

Identification of genomic alterations acquired during treatment with EGFR-TKIs in non-small cell lung cancer. / Kubo, Naoki; Harada, Taishi; Shiraishi, Yoshimasa; Nosaki, Kaname; Nakagaki, Noriaki; Takeshita, Masafumi; Ouchi, Hiroshi; Iwama, Eiji; Tanaka, Kentaro; Okamoto, Isamu; Sasaki, Hiroyuki; Nakanishi, Yoichi.

:: Anticancer research, 巻 39, 番号 2, 01.02.2019, p. 671-677.

研究成果: ジャーナルへの寄稿記事

Kubo, Naoki ; Harada, Taishi ; Shiraishi, Yoshimasa ; Nosaki, Kaname ; Nakagaki, Noriaki ; Takeshita, Masafumi ; Ouchi, Hiroshi ; Iwama, Eiji ; Tanaka, Kentaro ; Okamoto, Isamu ; Sasaki, Hiroyuki ; Nakanishi, Yoichi. / Identification of genomic alterations acquired during treatment with EGFR-TKIs in non-small cell lung cancer. :: Anticancer research. 2019 ; 巻 39, 番号 2. pp. 671-677.
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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.",
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AU - Kubo, Naoki

AU - Harada, Taishi

AU - Shiraishi, Yoshimasa

AU - Nosaki, Kaname

AU - Nakagaki, Noriaki

AU - Takeshita, Masafumi

AU - Ouchi, Hiroshi

AU - Iwama, Eiji

AU - Tanaka, Kentaro

AU - Okamoto, Isamu

AU - Sasaki, Hiroyuki

AU - Nakanishi, Yoichi

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AB - 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.

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