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Pathology & Oncology Research

, Volume 25, Issue 2, pp 711–721 | Cite as

Early Hereditary Diffuse Gastric Cancer (eHDGC) is Characterized by Subtle Genomic Instability and Active DNA Damage Response

  • Soroush Nasri
  • Bostjan Humara
  • Ahmad Anjomshoaa
  • Nourodin Moradi
  • Naghmeh GholipourEmail author
  • Sakineh Mashjoor
  • Peng Zhang
Original Article

Abstract

Diffuse gastric cancer (DGC) is one of the two primary types of stomach cancer. Carriers of germline mutations in the gene encoding E-cadherin are predisposed to DGC. The primary aim of the present study was to determine if genomic instability is an early event in DGC and how it may lead to disease progression. Chromosomal aberrations in early intramucosal hereditary diffuse gastric cancer (eHDGC) were assessed using array comparative genomic hybridization (array CGH). Notably, no aneuploidy or other large-scale chromosomal rearrangements were detected. Instead, all aberrations affected small regions (< 4.8 Mb) and were predominantly deletions. Analysis of DNA sequence patterns revealed that essentially all aberrations possessed the characteristics of common fragile sites. These results and the results of subsequent immunohistochemical examinations demonstrated that unlike advanced DGC, eHDGCs is characterized by low levels of genomic instability at fragile sites. Furthermore, they express an active DNA damage response, providing a molecular basis for the observed indolence of eHDGC. This finding is an important step to understanding the pathology underlying natural history of DGC and supports a revision of the current definition of eHDGC as a malignant disease.

Keywords

Genomic instability Diffuse gastric cancer Array CGH DNA fragility 

Notes

Acknowledgements

This research was supported by HS and JC Anderson Charitable Trust and the Health Research Council of New Zealand.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

Supplementary material

12253_2018_547_MOESM1_ESM.docx (26 kb)
ESM 1 (DOCX 25 kb)

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Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  • Soroush Nasri
    • 1
    • 2
  • Bostjan Humara
    • 1
  • Ahmad Anjomshoaa
    • 1
    • 3
  • Nourodin Moradi
    • 2
  • Naghmeh Gholipour
    • 2
    • 4
    Email author
  • Sakineh Mashjoor
    • 5
  • Peng Zhang
    • 6
  1. 1.Cancer Genetics Laboratory, Department of BiochemistryUniversity of OtagoDunedinNew Zealand
  2. 2.Milad Center for Medical GeneticsSariIran
  3. 3.Department of Medical Genetics, Faculty of MedicineKerman University of Medical SciencesKermanIran
  4. 4.Department of Medical GeneticsNational Institute of Genetic Engineering and BiotechnologyTehranIran
  5. 5.Department of Marine biology, Faculty of Marine Science and TechnologyHormozgan UniversityBandar AbbasIran
  6. 6.Division of Biomedical Science and Biochemistry, Research School of Biology, ANU College of Medicine, Biology and EnvironmentAustralian National UniversityCanberraAustralia

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