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Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing
BACKGROUND: Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. METHODS: In this study, we established a hybridization capture-based NGS panel including...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549266/ https://www.ncbi.nlm.nih.gov/pubmed/31164161 http://dx.doi.org/10.1186/s12967-019-1941-0 |
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author | Cai, Hui Jing, Changqing Chang, Xusheng Ding, Dan Han, Ting Yang, Junchi Lu, Zhengmao Hu, Xuguang Liu, Zhaorui Wang, Jinshen Shang, Liang Wu, Shouxin Meng, Peng Lin, Ling Zhao, Jiangman Nie, Mingming Yin, Kai |
author_facet | Cai, Hui Jing, Changqing Chang, Xusheng Ding, Dan Han, Ting Yang, Junchi Lu, Zhengmao Hu, Xuguang Liu, Zhaorui Wang, Jinshen Shang, Liang Wu, Shouxin Meng, Peng Lin, Ling Zhao, Jiangman Nie, Mingming Yin, Kai |
author_sort | Cai, Hui |
collection | PubMed |
description | BACKGROUND: Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. METHODS: In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data. RESULTS: 35 significantly mutated genes were identified such as TP53, AKAP9, DRD2, PTEN, CDH1, LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e−5), differentiation (1.9e−7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database. CONCLUSIONS: We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1941-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6549266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65492662019-06-06 Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing Cai, Hui Jing, Changqing Chang, Xusheng Ding, Dan Han, Ting Yang, Junchi Lu, Zhengmao Hu, Xuguang Liu, Zhaorui Wang, Jinshen Shang, Liang Wu, Shouxin Meng, Peng Lin, Ling Zhao, Jiangman Nie, Mingming Yin, Kai J Transl Med Research BACKGROUND: Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. METHODS: In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data. RESULTS: 35 significantly mutated genes were identified such as TP53, AKAP9, DRD2, PTEN, CDH1, LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e−5), differentiation (1.9e−7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database. CONCLUSIONS: We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1941-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-04 /pmc/articles/PMC6549266/ /pubmed/31164161 http://dx.doi.org/10.1186/s12967-019-1941-0 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Cai, Hui Jing, Changqing Chang, Xusheng Ding, Dan Han, Ting Yang, Junchi Lu, Zhengmao Hu, Xuguang Liu, Zhaorui Wang, Jinshen Shang, Liang Wu, Shouxin Meng, Peng Lin, Ling Zhao, Jiangman Nie, Mingming Yin, Kai Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing |
title | Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing |
title_full | Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing |
title_fullStr | Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing |
title_full_unstemmed | Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing |
title_short | Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing |
title_sort | mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549266/ https://www.ncbi.nlm.nih.gov/pubmed/31164161 http://dx.doi.org/10.1186/s12967-019-1941-0 |
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