Novel Somatic Variants in CTNNA1 Gene in Iranian Patients with Diffuse Gastric Cancer

Aim: Here we aimed to evaluate somatic mutations of CTNNA1 in DGC patients. Background: Diffuse gastric cancer (DGC) is one of the main types of gastric cancer which most of the cases are sporadic diffuse gastric cancer (SDGC). It has been shown that mutations in CTNNA1 are responsible for some cases of hereditary diffuse gastric cancer (HDGC). Methods: In the present work, 48 formalin-fixed paraffin-embedded tissues, including samples of 38 SDGC and 10 HDGC patients were examined by performing Sanger sequencing approach on PCR products amplified from 18 exons and boundaries of intron/exon of CTNNA1 gene. Results: We revealed 9 novel mutations in the CTNNA1 gene in patients with HDGC and SDGC, from which one variant was intronic. Eight patients had at least one disease-causing mutation (16.6%). Most of the patients were in the III stage of cancer (50%). Except for one patient, histological type of the rest of mutation-harboring patients was signet ring cell carcinoma, and only one HDGC patient had CTNNA1 mutation. Conclusion: Our study showed several novel variants in the CTNNA1 gene in Iranian DGC patients, and implies the potential role of ?-catenin in the pathogenesis of SDGC, as well as HDGC.