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New Variants in the CDH1 Gene in Iranian Families with Hereditary Diffuse Gastric Cancer

Document Type : Original Article(s)

Authors

1 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

2 Department of Genetics and Molecular Biology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran

3 Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

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 17 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 16 exons and exon/intron boundaries of the CDH1 gene and exon 2 of CTNNA1 gene. The Multiplex Ligation-dependent Probe Amplification technique was performed on patients with no pathogenic variants in sequencing.
Results: Totally, 17 probands comprising seven males and 10 females were assessed. In three patients, we recognized the tumors in the early TNM stage (I, II), while in 14 cases, tumors were observed in the late stages (III, IV). Overall, DNA sequencing of the CDH1 gene identified 16 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 1 of two patients.
Conclusion: Our results showed that E-cadherin deficiency in HDGC was related to CDH1 gene point mutations and large deletion with high heterogeneity, which should be considered in the diagnosis and treatment of HDGC patients.

Keywords

Full Text

How to cite this article:

Kheirollahi M, Saneipour M, Tabatabaiefar MA, Zeinalian M, Minakari M, Moridnia A. New variants in the CDH1 gene in Iranian families with hereditary diffuse gastric cancer. Middle East J Cancer. 2020;11(4): 493-501. doi: 10. 30476/mejc.2020.81478.1016.

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Middle East Journal of Cancer
Volume 11, Issue 4 - Serial Number 44
October 2020
Pages 493-501
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