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

Nat Commun. 2018 Jun 30;9(1):2447. doi: 10.1038/s41467-018-04907-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Signet Ring Cell / drug therapy
  • Carcinoma, Signet Ring Cell / genetics*
  • Cell Line, Tumor
  • Claudins / genetics*
  • Claudins / physiology
  • Drug Resistance, Neoplasm / genetics
  • Female
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / physiology
  • Humans
  • Male
  • Mutant Chimeric Proteins*
  • Oxaliplatin / therapeutic use
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Treatment Outcome
  • Whole Genome Sequencing


  • ARHGAP26 protein, human
  • Antineoplastic Agents
  • CLDN18 protein, human
  • Claudins
  • GTPase-Activating Proteins
  • Mutant Chimeric Proteins
  • Oxaliplatin