Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer

Yang Shu, Weihan Zhang, Qianqian Hou, Linyong Zhao, Shouyue Zhang, Jiankang Zhou, Xiaohai Song, Yan Zhang, Dan Jiang, Xinzu Chen, Peiqi Wang, Xuyang Xia, Fei Liao, Dandan Yin, Xiaolong Chen, Xueyan Zhou, Duyu Zhang, Senlin Yin, Kun Yang, Jianping Liu, Leilei Fu, Lan Zhang, Yuelan Wang, Junlong Zhang, Yunfei An, Hua Cheng, Bin Zheng, Hongye Sun, Yinglan Zhao, Yongsheng Wang, Dan Xie, Liang Ouyang, Ping Wang, Wei Zhang, Meng Qiu, Xianghui Fu, Lunzhi Dai, Gu He, Hanshuo Yang, Wei Cheng, Li Yang, Bo Liu, Weimin Li, Biao Dong, Zongguang Zhou, Yuquan Wei, Yong Peng (), Heng Xu () and Jiankun Hu ()
Additional contact information
Yang Shu: Sichuan University and Collaborative Innovation Center
Weihan Zhang: Sichuan University and Collaborative Innovation Center
Qianqian Hou: Sichuan University and Collaborative Innovation Center
Linyong Zhao: Sichuan University and Collaborative Innovation Center
Shouyue Zhang: Sichuan University and Collaborative Innovation Center
Jiankang Zhou: Sichuan University and Collaborative Innovation Center
Xiaohai Song: Sichuan University and Collaborative Innovation Center
Yan Zhang: Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Dan Jiang: West China Hospital, Sichuan University
Xinzu Chen: Sichuan University and Collaborative Innovation Center
Peiqi Wang: Sichuan University
Xuyang Xia: Sichuan University and Collaborative Innovation Center
Fei Liao: Sichuan University and Collaborative Innovation Center
Dandan Yin: Sichuan University and Collaborative Innovation Center
Xiaolong Chen: Sichuan University and Collaborative Innovation Center
Xueyan Zhou: Sichuan University and Collaborative Innovation Center
Duyu Zhang: Sichuan University and Collaborative Innovation Center
Senlin Yin: Sichuan University and Collaborative Innovation Center
Kun Yang: Sichuan University and Collaborative Innovation Center
Jianping Liu: West China Hospital, Sichuan University
Leilei Fu: Sichuan University and Collaborative Innovation Center
Lan Zhang: Sichuan University and Collaborative Innovation Center
Yuelan Wang: Sichuan University and Collaborative Innovation Center
Junlong Zhang: West China Hospital, Sichuan University
Yunfei An: West China Hospital, Sichuan University
Hua Cheng: WuxiNextCODE
Bin Zheng: WuxiNextCODE
Hongye Sun: WuxiNextCODE
Yinglan Zhao: Sichuan University and Collaborative Innovation Center
Yongsheng Wang: Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Dan Xie: Sichuan University and Collaborative Innovation Center
Liang Ouyang: Sichuan University and Collaborative Innovation Center
Ping Wang: Albert Einstein College of Medicine
Wei Zhang: Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University
Meng Qiu: Cancer Center, West China Hospital, Sichuan University
Xianghui Fu: Sichuan University and Collaborative Innovation Center
Lunzhi Dai: Sichuan University and Collaborative Innovation Center
Gu He: Sichuan University and Collaborative Innovation Center
Hanshuo Yang: Sichuan University and Collaborative Innovation Center
Wei Cheng: Sichuan University and Collaborative Innovation Center
Li Yang: Sichuan University and Collaborative Innovation Center
Bo Liu: Sichuan University and Collaborative Innovation Center
Weimin Li: West China Hospital, Sichuan University
Biao Dong: Sichuan University and Collaborative Innovation Center
Zongguang Zhou: Sichuan University and Collaborative Innovation Center
Yuquan Wei: Sichuan University and Collaborative Innovation Center
Yong Peng: Sichuan University and Collaborative Innovation Center
Heng Xu: Sichuan University and Collaborative Innovation Center
Jiankun Hu: Sichuan University and Collaborative Innovation Center

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04907-0

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