Novel Variants and Copy Number Variation in CDH1 Gene in Iranian Patients with Sporadic Diffuse Gastric Cancer

  • Abbas Moridnia
  • Mohammad Amin Tabatabaiefar
  • Mehrdad Zeinalian
  • Mohammad Minakari
  • Majid Kheirollahi
  • Noushin Afshar Moghaddam
Original Research



The aim of this study was to survey the nucleotide changes and copy number variations (CNV) in the CDH1 gene in Iranian patients with sporadic diffuse gastric cancer (SDGC).

Materials and Methods

In this study, 28 patients were examined who upon gastrectomy had been diagnosed with SDGC according to the familial history and histopathological criteria which was confirmed by the pathologist. DNA extraction was performed from formalin-fixed paraffin-embedded tissues using a phenol-chloroform method following xylene deparaffinization. Determination of DNA sequence by Sanger was performed using PCR amplification of 16 exons and boundaries of intron/exon of CDH1 gene. Multiplex ligation-dependent probe amplification (MLPA) was performed on patients with pathogenic disorders in the sequence.


In total, patients included 20 males and 8 females. Of all patients, 12 patients were under 45 years old (early onset gastric cancer, EODC) and 16 patients were older. The tumor was diagnosed in the early TNM stage (I, II) in six patients and in late stages (III, IV) in 19 cases. Altogether, 16 variants (three exonic with one new variant and 13 intronic with nine new variants) were found in DNA sequencing of the CDH1 gene in five samples. Also, using MLPA, a new duplication in exon 9 and one deletion in exon 2 were detected in two other patients. Altogether, CDH1 variants were identified in seven out of 28 patients (25%).


Our study revealed several novel somatic variants in the CDH1 gene in Iranian patients with sporadic diffuse GC. Our data supports the hypothesis that mutations in CDH1 gene, and particularly the mutations we describe, should be considered, even in sporadic cases of gastric cancer. The presence of these mutations in patients raises important issues regarding genetic counseling and diagnostic test in DGC patients.


Sporadic Diffuse gastric cancer CDH1 Variant Iran 



We sincerely thank the patients and the professional staff of the pathology lab in Al-Zahra hospital (Isfahan, Iran) and also Alaa cancer control center (Isfahan, Iran) for their cooperation in this study.

Funding Information

This research was supported by Isfahan University of Medical Sciences, Isfahan, Iran, with grant number 394479.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Ethical Approval

In this study, all procedures followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable disease and Department of Genetics and Molecular Biology, School of MedicineIsfahan University of Medical SciencesIsfahanIran
  2. 2.Internal medicine department, School of MedicineIsfahan University of Medical SciencesIsfahanIran
  3. 3.Department of Pathology, School of MedicineIsfahan University of Medical SciencesIsfahanIran

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