Please use this identifier to cite or link to this item:
Title: Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing
Authors: Nahar, Rahul
Zhai, Weiwei
Zhang, Tong
Takano, Angela
Khng, Alexis J.
Lee, Yin Yeng
Liu, Xingliang
Lim, Chong Hee
Koh, Tina P. T.
Aung, Zaw Win
Lim, Tony Kiat Hon
Veeravalli, Lavanya
Yuan, Ju
Teo, Audrey S. M.
Chan, Cheryl X.
Poh, Huay Mei
Chua, Ivan M. L.
Liew, Audrey Ann
Lau, Dawn Ping Xi
Kwang, Xue Lin
Toh, Chee Keong
Lim, Wan-Teck
Lim, Bing
Tam, Wai Leong
Tan, Eng-Huat
Hillmer, Axel M.
Tan, Daniel S. W.
Keywords: Genomic
Issue Date: 2018
Source: Nahar, R., Zhai, W., Zhang, T., Takano, A., Khng, A. J., Lee, Y. Y., et al. (2018). Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing. Nature Communications, 9(1), 216-.
Series/Report no.: Nature Communications
Abstract: EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability, and low background mutation rates.
DOI: 10.1038/s41467-017-02584-z
Rights: © 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles


Updated on Sep 4, 2020


Updated on Jan 14, 2021

Page view(s)

Updated on Jan 18, 2021


Updated on Jan 18, 2021

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.