Majid Kheirollahi - Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease and Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Maryam Saneipour - Department of Genetics and Molecular Biology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran
Mohammad Amin Tabatabaiefar - Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease and Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mehrdad Zeinalian - Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease and Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Mohammad Minakari - Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abbas Moridnia - Department of Genetics and Molecular Biology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran

Background: Hereditary diffuse gastric cancer (HDGC) is a hereditable form of diffuse gastric cancer with very aggressive tumors, poor prognosis, and delayed clinical signs. Method: We assessed ۱۷ probands identified with HDGC upon gastrectomy according to the histopathological criteria confirmed by a pathologist and familial history. We extracted DNA from peripheral blood and formalin fixed paraffin-embedded tissues. DNA sequencing was done following PCR amplification of ۱۶ exons and exon/intron boundaries of the CDH۱ gene and exon ۲ of CTNNA۱ gene. The Multiplex Ligation-dependent Probe Amplification technique was performed on patients with no pathogenic variants in sequencing. Results: Totally, ۱۷ probands comprising seven males and ۱۰ females were assessed. In three patients, we recognized the tumors in the early TNM stage (I, II), while in ۱۴ cases, tumors were observed in the late stages (III, IV). Overall, DNA sequencing of the CDH۱ gene identified ۱۶ variants (seven exonic including five new variants and nine intronic containing six new variants). Moreover, Multiplex Ligation-dependent Probe Amplification detected one deletion in exon ۱ of two patients. Conclusion: Our results showed that E-cadherin deficiency in HDGC was related to CDH۱ gene point mutations and large deletion with high heterogeneity, which should be considered in the diagnosis and treatment of HDGC patients.

CDH۱ gene, Diffuse Gastric Cancer, Iranian families, Hereditary, Mutation