Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.
Yang ShuWeihan ZhangQianqian HouLinyong ZhaoShouyue ZhangJiankang ZhouXiaohai SongYan ZhangDan JiangXinzu ChenPeiqi WangXuyang XiaFei LiaoDandan YinXiaolong ChenXueyan ZhouDuyu ZhangSenlin YinKun YangJianping LiuLeilei FuLan ZhangYuelan WangJunlong ZhangYunfei AnHua ChengBin ZhengHongye SunYinglan ZhaoYongsheng WangDan XieLiang OuyangPing WangWei ZhangMeng QiuXianghui FuLunzhi DaiGu HeHanshuo YangWei ChengLi YangBo LiuWeimin LiBiao DongZongguang ZhouYuquan WeiYong PengHeng XuJiankun HuPublished in: Nature communications (2018)
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.
Keyphrases
- locally advanced
- single cell
- end stage renal disease
- risk factors
- cell therapy
- induced apoptosis
- newly diagnosed
- copy number
- photodynamic therapy
- chronic kidney disease
- squamous cell carcinoma
- peritoneal dialysis
- radiation therapy
- rectal cancer
- papillary thyroid
- stem cells
- prognostic factors
- cell cycle arrest
- mesenchymal stem cells
- oxidative stress
- gene expression
- signaling pathway
- patient reported outcomes
- cell death
- bone marrow
- dna methylation
- pi k akt
- endoplasmic reticulum stress