Project description:Signet ring cell carcinoma (SRCC) of the stomach is a subtype of gastric cancer with poor prognosis. It is characterized with unique large vacuoles of mucin and compressed nucleus, which resemble signet rings, while the underlying molecular mechanisms driving SRCC remain elusive. Here, we studied whether and how human gastric SRCC-associated ARID1A deficiency drove the disease.
Project description:Signet ring cell carcinoma (SRCC) of the stomach is a subtype of gastric cancer with poor prognosis. It is characterized with unique large vacuoles of mucin and compressed nucleus, which resemble signet rings, while the underlying molecular mechanisms driving SRCC remain elusive. Here, we studied whether and how human gastric SRCC-associated ARID1A deficiency drove the disease.
Project description:Signet ring cell carcinoma (SRCC) of the stomach is a subtype of gastric cancer with poor prognosis. It is characterized with unique large vacuoles of mucin and compressed nucleus, which resemble signet rings, while the underlying molecular mechanisms driving SRCC remain elusive. Here, we studied whether and how human gastric SRCC-associated ARID1A deficiency drove the disease.
Project description:This experiment was performed to compare and intend to acquire a genetic expression feature of signet ring cell carcinoma in colorectal cancer that is extremely rare histological type and also shows significantly worse prognosis compared with conventional histological type of the cancer.
Project description: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.
