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Nat Commun. 2018 Jun 30;9(1):2447. doi: 10.1038/s41467-018-04907-0.

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

Author information

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.
3
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China.
4
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
5
Department of Pathology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
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.
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.
12
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China.
13
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China. pengyong10@hotmail.com.
14
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. xuheng81916@scu.edu.cn.
15
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 610041, Chengdu, Sichuan, China. xuheng81916@scu.edu.cn.
16
Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China. xuheng81916@scu.edu.cn.
17
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. hujkwch@126.com.

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.

PMID:
29961079
PMCID:
PMC6026495
DOI:
10.1038/s41467-018-04907-0
[Indexed for MEDLINE]
Free PMC Article

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