Comparative Study on Mutations in CDH1 Gene in Iranian Patients with Hereditary Diffuse Gastric Cancer (HDGC) and Sporadic Diffuse Gastric Cancer (SDGC)

Background: Gastric cancer (GC) is the fourth common cancer worldwide and the second cause of mortality among all cancers. Mutations in the CDH1 gene are the most common cause of hereditary diffuse gastric cancer (HDGC) and sporadic diffuse gastric cancer (SDGC). CDH1 gene encode for E-cadherin protein. We compared the nucleotide alterations and copy number variations in CDH1 gene between Iranian patients with HDGC and SDGC. Methods: We evaluated 45 patients including 17 cases with HDGC and 28 cases with SDGC identified according to the histopathological criteria and familial history. DNA extraction was obtained from peripheral blood and formalin-fixed paraffin-embedded (FFPE) tissues. The DNA sequencing was completed using polymerase chain reaction (PCR) amplification of 16 exons of the CDH1 gene. Multiplex ligation-dependent probe amplification (MLPA) method was accomplished on samples with no pathogenic variants in sequencing. Findings: Synonymous substitution of L116L and A692A was detected in patients with HDGC and SDGC; but non-synonymous substitution of D777E, c.889delA, and c.1177delA deletions only detected in patients with HDGC. MLPA results revealed one deletion in exon 1 of CDH1 gene in patients with HDGC and one deletion in exon 2, and one duplication in exon 9 of CDH1 gene in patients with SDGC. Conclusion: According to the results, different variants in CDH1 gene was presented in patients with HDGC and SDGC that emphasis the survey of CDH1 variants and especially detected variants in this study in the diagnosis of diffuse gastric cancer disease.