Abstract

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.

Details

Title
Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer
Author
Yang, Shu 1 ; Zhang, Weihan 2 ; Hou, Qianqian 3 ; Zhao, Linyong 2 ; Zhang, Shouyue 3 ; Zhou, Jiankang 4 ; Song, Xiaohai 2 ; Zhang, Yan 5 ; Jiang, Dan 6 ; Chen, Xinzu 2 ; Wang, Peiqi 7 ; Xia, Xuyang 3 ; Liao, Fei 3 ; Yin, Dandan 3 ; Chen, Xiaolong 2 ; Zhou, Xueyan 3 ; Zhang, Duyu 3 ; Yin, Senlin 4 ; Yang, Kun 2 ; Liu, Jianping 6 ; Fu, Leilei 4 ; Zhang, Lan 4 ; Wang, Yuelan 3 ; Zhang, Junlong 8 ; An, Yunfei 8 ; Cheng, Hua 9 ; Zheng, Bin 9 ; Sun, Hongye 9 ; Zhao, Yinglan 4 ; Wang, Yongsheng 5 ; Xie, Dan 10 ; Ouyang, Liang 4 ; Wang, Ping 11 ; Zhang, Wei 12 ; Qiu, Meng 13 ; Fu, Xianghui 4 ; Dai, Lunzhi 4 ; Gu, He 4   VIAFID ORCID Logo  ; Yang, Hanshuo 4 ; Cheng, Wei 4 ; Yang, Li 4 ; Liu, Bo 4 ; Li, Weimin 14 ; Dong, Biao 4 ; Zhou, Zongguang 2 ; Wei, Yuquan 4 ; Peng, Yong 4 ; Xu, Heng 15   VIAFID ORCID Logo  ; Hu, Jiankun 2 

1  Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China; 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, Chengdu, Sichuan, China 
2  Department of Gastrointestinal Surgery, Institute of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China 
3  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, Chengdu, Sichuan, China 
4  State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China 
5  Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China 
6  Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China 
7  State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China 
8  Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China 
9  WuxiNextCODE, Shanghai, China 
10  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, Chengdu, Sichuan, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China 
11  Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA 
12  Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha, China 
13  Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China 
14  Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China 
15  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, Chengdu, Sichuan, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China; Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China 
Pages
1-11
Publication year
2018
Publication date
Jun 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-04907-0
ProQuest document ID
2062130289
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.