CDH۱ germline mutation in hereditary diffuse gastric cancer: a multicenter study

Background and Aim: Hereditary diffuse gastric cancer (HDGC) is an inherited form of gastric cancer which is characterized by increasing the risk of developing both gastric and lobular breast cancer. CDH۱ germline mutations account for about ۳۰-۵۰% of HDGC. Because of its high penetrance and autosomal dominant inheritance pattern the National Comprehensive Cancer Network (NCCN) has developed criteria to facilitate the identification of CDH۱ mutation carriers. Since prophylactic gastrectomy is a recommended treatment for CDH۱ mutation carriers, therefore, genetic testing should be undertaken to confirm the diagnosis and allows for family surveillance. The aim of this study was to assess the frequency of CDH۱ germline mutations in Iranian patients with diffuse gastric cancer.Methods: We ascertained ۱۷ patients who met the NCCN criteria for genetic testing. The diffuse gastric cancer diagnosis was independently confirmed by ۲ pathologists. All the eligible participants were asked for a ۱۰-milliliter blood sample for DNA extraction. Screening for CDH۱ germline mutations was carried out by DNA sequencing.Results: In the study population, ۲ pathogenic missense mutations (۱۱.۷%), c.۲۲۷۵G>A and c.۲۱۹۵G>A, were identified in ۲ gastric patients who were both under ۴۰ at diagnosis. A variant of unknown significance, c.۲۱۴G>A, was also found in ۱ patient who is also under ۴۰.Conclusion: This study represents the significance of CDH۱ mutation screening as a surrogate predictor of hereditary diffuse gastric cancer that could be considered as an important step in treatment and management decisions.

Keywords:

CDH۱ mutation , Hereditary Diffuse Gastric Cancer , Prophylactic gastrectomy