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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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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. |
format | Online Article Text |
id | pubmed-5967326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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