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Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.
Shu, Yang; Zhang, Weihan; Hou, Qianqian; Zhao, Linyong; Zhang, Shouyue; Zhou, Jiankang; Song, Xiaohai; Zhang, Yan; Jiang, Dan; Chen, Xinzu; Wang, Peiqi; Xia, Xuyang; Liao, Fei; Yin, Dandan; Chen, Xiaolong; Zhou, Xueyan; Zhang, Duyu; Yin, Senlin; Yang, Kun; Liu, Jianping; Fu, Leilei; Zhang, Lan; Wang, Yuelan; Zhang, Junlong; An, Yunfei; Cheng, Hua; Zheng, Bin; Sun, Hongye; Zhao, Yinglan; Wang, Yongsheng; Xie, Dan; Ouyang, Liang; Wang, Ping; Zhang, Wei; Qiu, Meng; Fu, Xianghui; Dai, Lunzhi; He, Gu; Yang, Hanshuo; Cheng, Wei; Yang, Li; Liu, Bo; Li, Weimin; Dong, Biao; Zhou, Zongguang; Wei, Yuquan; Peng, Yong; Xu, Heng; Hu, Jiankun.
Affiliation
  • Shu Y; 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.
  • Zhang W; 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.
  • Hou Q; 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.
  • Zhao L; 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.
  • Zhang S; 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.
  • Zhou J; 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.
  • Song X; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Zhang Y; 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.
  • Jiang D; Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • Chen X; Department of Pathology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • Wang P; 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.
  • Xia X; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 610041, Chengdu, China.
  • Liao F; 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.
  • Yin D; 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.
  • Chen X; 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.
  • Zhou X; 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.
  • Zhang D; 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.
  • Yin S; 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.
  • Yang K; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Liu J; 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.
  • Fu L; Department of Pathology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • Zhang L; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Wang Y; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Zhang J; 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.
  • An Y; Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • Cheng H; Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • Zheng B; WuxiNextCODE, 200131, Shanghai, China.
  • Sun H; WuxiNextCODE, 200131, Shanghai, China.
  • Zhao Y; WuxiNextCODE, 200131, Shanghai, China.
  • Wang Y; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Xie D; Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • Ouyang L; 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.
  • Wang P; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Zhang W; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Qiu M; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
  • Fu X; Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, 410008, Changsha, China.
  • Dai L; Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • He G; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Yang H; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Cheng W; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Yang L; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Liu B; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Li W; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Dong B; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Zhou Z; Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
  • Wei Y; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Peng Y; 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.
  • Xu H; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
  • Hu J; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China. pengyong10@hotmail.com.
Nat Commun ; 9(1): 2447, 2018 06 30.
Article in En | MEDLINE | ID: mdl-29961079
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.
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Full text: 1 Database: MEDLINE Main subject: Stomach Neoplasms / Carcinoma, Signet Ring Cell / GTPase-Activating Proteins / Mutant Chimeric Proteins / Claudins Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans / Male Language: En Year: 2018 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Stomach Neoplasms / Carcinoma, Signet Ring Cell / GTPase-Activating Proteins / Mutant Chimeric Proteins / Claudins Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans / Male Language: En Year: 2018 Type: Article