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13.12.2018 | Original Article | Ausgabe 2/2019

Pathology & Oncology Research 2/2019

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

Pathology & Oncology Research > Ausgabe 2/2019
Soroush Nasri, Bostjan Humara, Ahmad Anjomshoaa, Nourodin Moradi, Naghmeh Gholipour, Sakineh Mashjoor, Peng Zhang
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s12253-018-0547-9) contains supplementary material, which is available to authorized users.


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.

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