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Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients

Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. Here, we present a comprehensive genomic landscape of 149 non-small cell lung cancer (NSCLC) cases and identify 15 potential driver genes. We...

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Autores principales: Wang, Cheng, Yin, Rong, Dai, Juncheng, Gu, Yayun, Cui, Shaohua, Ma, Hongxia, Zhang, Zhihong, Huang, Jiaqi, Qin, Na, Jiang, Tao, Geng, Liguo, Zhu, Meng, Pu, Zhening, Du, Fangzhi, Wang, Yuzhuo, Yang, Jianshui, Chen, Liang, Wang, Qianghu, Jiang, Yue, Dong, Lili, Yao, Yihong, Jin, Guangfu, Hu, Zhibin, Jiang, Liyan, Xu, Lin, Shen, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967326/
https://www.ncbi.nlm.nih.gov/pubmed/29799009
http://dx.doi.org/10.1038/s41467-018-04492-2
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author Wang, Cheng
Yin, Rong
Dai, Juncheng
Gu, Yayun
Cui, Shaohua
Ma, Hongxia
Zhang, Zhihong
Huang, Jiaqi
Qin, Na
Jiang, Tao
Geng, Liguo
Zhu, Meng
Pu, Zhening
Du, Fangzhi
Wang, Yuzhuo
Yang, Jianshui
Chen, Liang
Wang, Qianghu
Jiang, Yue
Dong, Lili
Yao, Yihong
Jin, Guangfu
Hu, Zhibin
Jiang, Liyan
Xu, Lin
Shen, Hongbing
author_facet Wang, Cheng
Yin, Rong
Dai, Juncheng
Gu, Yayun
Cui, Shaohua
Ma, Hongxia
Zhang, Zhihong
Huang, Jiaqi
Qin, Na
Jiang, Tao
Geng, Liguo
Zhu, Meng
Pu, Zhening
Du, Fangzhi
Wang, Yuzhuo
Yang, Jianshui
Chen, Liang
Wang, Qianghu
Jiang, Yue
Dong, Lili
Yao, Yihong
Jin, Guangfu
Hu, Zhibin
Jiang, Liyan
Xu, Lin
Shen, Hongbing
author_sort Wang, Cheng
collection PubMed
description Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. Here, we present a comprehensive genomic landscape of 149 non-small cell lung cancer (NSCLC) cases and identify 15 potential driver genes. We reveal that Chinese patients are specially characterized by not only highly clustered EGFR mutations but a mutational signature (MS3, 33.7%), that is associated with inflammatory tumor-infiltrating B lymphocytes (P = 0.001). The EGFR mutation rate is significantly increased with the proportion of the MS3 signature (P = 9.37 × 10(−5)). TCGA data confirm that the infiltrating B lymphocyte abundance is significantly higher in the EGFR-mutated patients (P = 0.007). Additionally, MS3-high patients carry a higher contribution of distant chromosomal rearrangements >1 Mb (P = 1.35 × 10(−7)), some of which result in fusions involving genes with important functions (i.e., ALK and RET). Thus, inflammatory infiltration may contribute to the accumulation of EGFR mutations, especially in never-smokers.
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spelling pubmed-59673262018-05-25 Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients Wang, Cheng Yin, Rong Dai, Juncheng Gu, Yayun Cui, Shaohua Ma, Hongxia Zhang, Zhihong Huang, Jiaqi Qin, Na Jiang, Tao Geng, Liguo Zhu, Meng Pu, Zhening Du, Fangzhi Wang, Yuzhuo Yang, Jianshui Chen, Liang Wang, Qianghu Jiang, Yue Dong, Lili Yao, Yihong Jin, Guangfu Hu, Zhibin Jiang, Liyan Xu, Lin Shen, Hongbing Nat Commun Article Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. Here, we present a comprehensive genomic landscape of 149 non-small cell lung cancer (NSCLC) cases and identify 15 potential driver genes. We reveal that Chinese patients are specially characterized by not only highly clustered EGFR mutations but a mutational signature (MS3, 33.7%), that is associated with inflammatory tumor-infiltrating B lymphocytes (P = 0.001). The EGFR mutation rate is significantly increased with the proportion of the MS3 signature (P = 9.37 × 10(−5)). TCGA data confirm that the infiltrating B lymphocyte abundance is significantly higher in the EGFR-mutated patients (P = 0.007). Additionally, MS3-high patients carry a higher contribution of distant chromosomal rearrangements >1 Mb (P = 1.35 × 10(−7)), some of which result in fusions involving genes with important functions (i.e., ALK and RET). Thus, inflammatory infiltration may contribute to the accumulation of EGFR mutations, especially in never-smokers. Nature Publishing Group UK 2018-05-24 /pmc/articles/PMC5967326/ /pubmed/29799009 http://dx.doi.org/10.1038/s41467-018-04492-2 Text en © The Author(s) 2018 Open Access 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/.
spellingShingle Article
Wang, Cheng
Yin, Rong
Dai, Juncheng
Gu, Yayun
Cui, Shaohua
Ma, Hongxia
Zhang, Zhihong
Huang, Jiaqi
Qin, Na
Jiang, Tao
Geng, Liguo
Zhu, Meng
Pu, Zhening
Du, Fangzhi
Wang, Yuzhuo
Yang, Jianshui
Chen, Liang
Wang, Qianghu
Jiang, Yue
Dong, Lili
Yao, Yihong
Jin, Guangfu
Hu, Zhibin
Jiang, Liyan
Xu, Lin
Shen, Hongbing
Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
title Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
title_full Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
title_fullStr Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
title_full_unstemmed Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
title_short Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
title_sort whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in chinese nsclc patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967326/
https://www.ncbi.nlm.nih.gov/pubmed/29799009
http://dx.doi.org/10.1038/s41467-018-04492-2
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