Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer
Menée en Chine à partir de l'analyse du génome entier d'échantillons tumoraux prélevés sur 1 868 patients atteints d'une linite gastrique puis menée à l'aide de 797 patients complémentaires et de lignées cellulaires, cette étude évalue l'association entre la présence du gène de fusion CLDN18-ARHGAP26/6 et le pronostic ou la réponse à une chimiothérapie à base d'oxaliplatine-fluoropyrimidines
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.
Nature Communications , résumé, 2018