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• Targeting the PI3K/Akt signaling pathway in gastric carcinoma: a reality for personalized medicine?

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         headline:Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing
         description: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. 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. 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. We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.
         datePublished:2019-06-04T00:00:00Z
         dateModified:2019-06-04T00:00:00Z
         pageStart:1
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            Gastric cancer
            Next-generation sequencing
            Tumor mutation burden
            Clinical actionable alterations
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            general
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      headline:Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing
      description: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. 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. 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. We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.
      datePublished:2019-06-04T00:00:00Z
      dateModified:2019-06-04T00:00:00Z
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      pageEnd:12
      license:http://creativecommons.org/publicdomain/zero/1.0/
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         Gastric cancer
         Next-generation sequencing
         Tumor mutation burden
         Clinical actionable alterations
         Biomedicine
         general
         Medicine/Public Health
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         name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Hui Cai
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Changqing Jing
      affiliation:
            name:Shandong Provincial Hospital Affiliated to Shandong University
            address:
               name:Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
               type:PostalAddress
            type:Organization
      name:Xusheng Chang
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Dan Ding
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Ting Han
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Junchi Yang
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Zhengmao Lu
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Xuguang Hu
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Zhaorui Liu
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Jinshen Wang
      affiliation:
            name:Shandong Provincial Hospital Affiliated to Shandong University
            address:
               name:Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
               type:PostalAddress
            type:Organization
      name:Liang Shang
      affiliation:
            name:Shandong Provincial Hospital Affiliated to Shandong University
            address:
               name:Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
               type:PostalAddress
            type:Organization
      name:Shouxin Wu
      affiliation:
            name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd.
            address:
               name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Zhangjiang Institute of Medical Innovation
            address:
               name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Peng Meng
      affiliation:
            name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd.
            address:
               name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Zhangjiang Institute of Medical Innovation
            address:
               name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Ling Lin
      affiliation:
            name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd.
            address:
               name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Zhangjiang Institute of Medical Innovation
            address:
               name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Jiangman Zhao
      affiliation:
            name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd.
            address:
               name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
               type:PostalAddress
            type:Organization
            name:Shanghai Zhangjiang Institute of Medical Innovation
            address:
               name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Mingming Nie
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Kai Yin
      url:http://orcid.org/0000-0002-1767-5210
      affiliation:
            name:The Second Military Medical University
            address:
               name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
      name:Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
      name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
      name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
      name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
      name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
      name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
      name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
      name:Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China
      name:Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China
      name:Department of Gastrointestinal Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China

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