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- Title
Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.
- Authors
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
- 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.
- Subjects
CANCER; EPIDEMIOLOGY; CARCINOGENESIS; CANCER patients; FLUOROPYRIMIDINES
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04907-0