Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma

Seijiro Sato, Masayuki Nagahashi, Terumoto Koike, Hiroshi Ichikawa, Yoshifumi Shimada, Satoshi Watanabe, Toshiaki Kikuchi, Kazuki Takada, Ryota Nakanishi, Eiji Oki, Tatsuro Okamoto, Kouhei Akazawa, Stephen Lyle, Yiwei Ling, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai, Masanori Tsuchida

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Abstract

Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease.

Original languageEnglish
Article number18560
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Atlases
Mutation
Genome
Neoplasms
Neoplasm Genes
Point Mutation
Genes
Adenocarcinoma of lung
Exons
Lung Neoplasms
Cell Cycle
Therapeutics

All Science Journal Classification (ASJC) codes

  • General

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Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma. / Sato, Seijiro; Nagahashi, Masayuki; Koike, Terumoto; Ichikawa, Hiroshi; Shimada, Yoshifumi; Watanabe, Satoshi; Kikuchi, Toshiaki; Takada, Kazuki; Nakanishi, Ryota; Oki, Eiji; Okamoto, Tatsuro; Akazawa, Kouhei; Lyle, Stephen; Ling, Yiwei; Takabe, Kazuaki; Okuda, Shujiro; Wakai, Toshifumi; Tsuchida, Masanori.

In: Scientific reports, Vol. 8, No. 1, 18560, 01.12.2018.

Research output: Contribution to journalArticle

Sato, S, Nagahashi, M, Koike, T, Ichikawa, H, Shimada, Y, Watanabe, S, Kikuchi, T, Takada, K, Nakanishi, R, Oki, E, Okamoto, T, Akazawa, K, Lyle, S, Ling, Y, Takabe, K, Okuda, S, Wakai, T & Tsuchida, M 2018, 'Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma', Scientific reports, vol. 8, no. 1, 18560. https://doi.org/10.1038/s41598-017-18560-y
Sato, Seijiro ; Nagahashi, Masayuki ; Koike, Terumoto ; Ichikawa, Hiroshi ; Shimada, Yoshifumi ; Watanabe, Satoshi ; Kikuchi, Toshiaki ; Takada, Kazuki ; Nakanishi, Ryota ; Oki, Eiji ; Okamoto, Tatsuro ; Akazawa, Kouhei ; Lyle, Stephen ; Ling, Yiwei ; Takabe, Kazuaki ; Okuda, Shujiro ; Wakai, Toshifumi ; Tsuchida, Masanori. / Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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