机构：[1]Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.四川大学华西医院[2]Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041 Chengdu, Sichuan, China.四川大学华西医院[3]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041 Chengdu, Sichuan, China.四川大学华西医院[4]Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.四川大学华西医院[5]Department of Pathology, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.四川大学华西医院[6]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 610041 Chengdu, China.[7]Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.四川大学华西医院[8]WuxiNextCODE, 200131 Shanghai, China.[9]Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.[10]Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, 410008 Changsha, China.[11]Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.四川大学华西医院[12]Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.四川大学华西医院
Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.
基金：
This work was supported by (1) National Key Research and Development
Program of China (No. 2016YFC0905000 [2016YFC0905002], No. 2016YFC0906000
and No. 2017YFC0909300); (2) National Natural Science Foundation of China
(No. 81522028, No. 81673452, No. 81400120, and No. 81402561); (3) Sichuan
Province Youth Science and Technology Innovative Research Team (No. 2015TD0009);
(4) 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan
University; (5) Young Scientist start fund of Sichuan University (No. 2015SCU04A44).
Heng Xu, Lunzhi Dai, Wei Cheng, and Dan Xie are supported by the grant from
"The Recruitment Program of Global Young Experts” (known as “the Thousand Young
Talents Plan”)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区综合性期刊
小类|2 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.[2]Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041 Chengdu, Sichuan, China.
共同第一作者：
通讯作者：
通讯机构：[2]Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine, Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041 Chengdu, Sichuan, China.[3]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041 Chengdu, Sichuan, China.[7]Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.
推荐引用方式(GB/T 7714)：
Yang Shu,Weihan Zhang,Qianqian Hou,et al.Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.[J].Nature communications.2018,9(1):2447.doi:10.1038/s41467-018-04907-0.
APA：
Yang Shu,Weihan Zhang,Qianqian Hou,Linyong Zhao,Shouyue Zhang...&Jiankun Hu.(2018).Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer..Nature communications,9,(1)
MLA：
Yang Shu,et al."Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.".Nature communications 9..1(2018):2447
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