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

被引：122

作者：

Shu, Yang ^{[1
,2
,3
]}

Zhang, Weihan ^{[1
,2
]}

Hou, Qianqian ^{[2
,3
]}

Zhao, Linyong ^{[1
,2
,4
]}

Zhang, Shouyue ^{[2
,3
]}

Zhou, Jiankang ^{[2
]}

Song, Xiaohai ^{[1
,2
]}

Zhang, Yan ^{[5
]}

Jiang, Dan ^{[6
]}

Chen, Xinzu ^{[1
,2
]}

Wang, Peiqi ^{[7
]}

Xia, Xuyang ^{[2
,3
]}

Liao, Fei ^{[2
,3
]}

Yin, Dandan ^{[2
,3
]}

Chen, Xiaolong ^{[1
,2
]}

Zhou, Xueyan ^{[2
,3
]}

Zhang, Duyu ^{[2
,3
]}

Yin, Senlin ^{[2
,4
]}

Yang, Kun ^{[1
,2
]}

Liu, Jianping ^{[6
]}

Fu, Leilei ^{[2
,4
]}

Zhang, Lan ^{[2
,4
]}

Wang, Yuelan ^{[2
,3
]}

Zhang, Junlong ^{[8
]}

An, Yunfei ^{[8
]}

Cheng, Hua ^{[9
]}

Zheng, Bin ^{[9
]}

Sun, Hongye ^{[9
]}

Zhao, Yinglan ^{[2
,4
]}

Wang, Yongsheng ^{[5
]}

Xie, Dan ^{[2
,3
,4
]}

Ouyang, Liang ^{[2
,4
]}

Wang, Ping ^{[10
]}

Zhang, Wei ^{[11
]}

Qiu, Meng ^{[12
]}

Fu, Xianghui ^{[2
,4
]}

Dai, Lunzhi ^{[2
,4
]}

He, Gu ^{[2
,4
]}

Yang, Hanshuo ^{[2
,4
]}

Cheng, Wei ^{[2
,4
]}

Yang, Li ^{[2
,4
]}

Liu, Bo ^{[2
,4
]}

Li, Weimin ^{[13
]}

Dong, Biao ^{[2
,4
]}

Zhou, Zongguang ^{[1
,2
]}

Wei, Yuquan ^{[2
,4
]}

Peng, Yong ^{[2
,4
]}

Xu, Heng ^{[2
,3
,4
,8
]}

Hu, Jiankun ^{[1
,2
]}

机构：

[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Dept Gastrointestinal Surg,Inst Gastr Canc, Chengdu 610041, Sichuan, Peoples R China

[2] Collaborat Innovat Ctr, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, State Key Lab Biotherapy & Precis Med, Precis Med Ctr, West China Hosp,Key Lab Sichuan Prov, Chengdu 610041, Sichuan, Peoples R China

[4] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China

[5] Sichuan Univ, West China Hosp, Dept Thorac Oncol, Canc Ctr,State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China

[6] Sichuan Univ, West China Hosp, Dept Pathol, Chengdu 610041, Sichuan, Peoples R China

[7] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China

[8] Sichuan Univ, West China Hosp, Dept Lab Med, Res Ctr,Clin Lab Med, Chengdu 610041, Sichuan, Peoples R China

[9] WuxiNextCODE, Shanghai 200131, Peoples R China

[10] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10461 USA

[11] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Hunan Key Lab Pharmacogenet, Changsha 410008, Hunan, Peoples R China

[12] Sichuan Univ, West China Hosp, Dept Abdominal Oncol, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China

[13] Sichuan Univ, West China Hosp, Dept Resp & Crit Care Med, Chengdu 610041, Sichuan, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

STRUCTURAL-VARIATION; ADENOCARCINOMA; MUTATIONS; GENOME; HISTOLOGY; CHEMOTHERAPY; LANDSCAPE; CARCINOMA; RESECTION; ADHESION;

D O I：

10.1038/s41467-018-04907-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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