WGS of 32 paired SRCC samples

Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however with no systematical investigation for prognostic genomic features. We systematically investigated the clinical characteristics of 1,868 Chinese gastric cancer patients, and found that signet-ring cell content was significantly related to multiple clinical characteristics and treatment outcomes. Next, we performed whole genome sequencing for 32 SRCC patients with > 80% signet-ring cells in tumor, and identified frequent5 CLDN18-ARHGAP26/6 fusion (25%). With additional 797 patients for validation, we notice that prevalence of CLDN18-ARHGAP26/6 fusion is positively associated with signet-ring cell content (P = 4.1 x 10 -9 ), younger age at diagnosis (P = 4.2 x 10 -10 ), female/male ratio (P = 1.7 x 10 -9 ), and advanced TNM stage (P = 1.7 x 10 -5 ). Importantly, patients with CLDN18-ARHGAP26/6 fusion had a worse survival outcomes (P = 0.03), and got no benefit0 from platinum/fluoropyrimidines based chemotherapy (P = 0.92) compared to fusion-free patients (P = 0.001), which is consistent with the fact of oxaliplatin/fluoropyrimidine resistance acquired in CLDN18-ARHGAP26 introduced gastric cancer cell lines. Overall, this study provides new insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001004045	Whole Genome Sequencing has been applied in 32 SRCC patients and the raw data have been subjected to standard procedures. Files with genomic variant calling were obtain at the last step.	HiSeq X Ten;ILLUMINA	64

Publications	Citations
Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer. Shu Y, Zhang W, Hou Q, Zhao L, Zhang S, Zhou J, Song X, Zhang Y, Jiang D, Chen X, Wang P, Xia X, Liao F, Yin D, Chen X, Zhou X, Zhang D, Yin S, Yang K, Liu J, Fu L, Zhang L, Wang Y, Zhang J, An Y, Cheng H, Zheng B, Sun H, Zhao Y, Wang Y, Xie D, Ouyang L, Wang P, Zhang W, Qiu M, Fu X, Dai L, He G, Yang H, Cheng W, Yang L, Liu B, Li W, Dong B, Zhou Z, Wei Y, Peng Y, Xu H, Hu J. Nat Commun 9: 2018 2447	79

Publications

Citations

Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer.
Shu Y, Zhang W, Hou Q, Zhao L, Zhang S, Zhou J, Song X, Zhang Y, Jiang D, Chen X, Wang P, Xia X, Liao F, Yin D, Chen X, Zhou X, Zhang D, Yin S, Yang K, Liu J, Fu L, Zhang L, Wang Y, Zhang J, An Y, Cheng H, Zheng B, Sun H, Zhao Y, Wang Y, Xie D, Ouyang L, Wang P, Zhang W, Qiu M, Fu X, Dai L, He G, Yang H, Cheng W, Yang L, Liu B, Li W, Dong B, Zhou Z, Wei Y, Peng Y, Xu H, Hu J. Nat Commun 9: 2018 2447