dc.contributor.authorNahar, Rahul
dc.contributor.authorZhai, Weiwei
dc.contributor.authorZhang, Tong
dc.contributor.authorTakano, Angela
dc.contributor.authorKhng, Alexis J.
dc.contributor.authorLee, Yin Yeng
dc.contributor.authorLiu, Xingliang
dc.contributor.authorLim, Chong Hee
dc.contributor.authorKoh, Tina P. T.
dc.contributor.authorAung, Zaw Win
dc.contributor.authorLim, Tony Kiat Hon
dc.contributor.authorVeeravalli, Lavanya
dc.contributor.authorYuan, Ju
dc.contributor.authorTeo, Audrey S. M.
dc.contributor.authorChan, Cheryl X.
dc.contributor.authorPoh, Huay Mei
dc.contributor.authorChua, Ivan M. L.
dc.contributor.authorLiew, Audrey Ann
dc.contributor.authorLau, Dawn Ping Xi
dc.contributor.authorKwang, Xue Lin
dc.contributor.authorToh, Chee Keong
dc.contributor.authorLim, Wan-Teck
dc.contributor.authorLim, Bing
dc.contributor.authorTam, Wai Leong
dc.contributor.authorTan, Eng-Huat
dc.contributor.authorHillmer, Axel M.
dc.contributor.authorTan, Daniel S. W.
dc.date.accessioned2018-07-25T06:51:22Z
dc.date.available2018-07-25T06:51:22Z
dc.date.issued2018
dc.identifier.citationNahar, 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-.en_US
dc.identifier.urihttp://hdl.handle.net/10220/45229
dc.description.abstractEGFR-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.en_US
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en_US
dc.description.sponsorshipNMRC (Natl Medical Research Council, S’pore)en_US
dc.format.extent11 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesNature Communicationsen_US
dc.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 http://creativecommons.org/licenses/by/4.0/.en_US
dc.subjectLungen_US
dc.subjectGenomicen_US
dc.titleElucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencingen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1038/s41467-017-02584-z
dc.description.versionPublished versionen_US


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