Gastroenterology

Gastroenterology

Volume 121, Issue 3, September 2001, Pages 612-618
Gastroenterology

Alimentary Tract
Distinct chromosomal aberrations in Epstein-Barr virus–carrying gastric carcinomas tested by comparative genomic hybridization

https://doi.org/10.1053/gast.2001.27200Get rights and content

Abstract

Background & Aims: Approximately 10% of gastric adenocarcinomas carry the human pathogenic Epstein-Barr virus (EBV). The role of EBV in the pathogenesis of these carcinomas remains to be established. Methods: To obtain a comprehensive overview of chromosomal aberrations in EBV-carrying and EBV-negative gastric carcinomas we performed comparative genomic hybridization (CGH) on 44 gastric carcinomas, 10 EBV-positive, and 34 EBV-negative. Additionally, DNA flow cytometry was done. Results: Loss of chromosome 4p (P < 0.001) and of 11p (P < 0.02) was exclusively restricted to EBV-carrying gastric carcinomas. In addition, loss of 18q (P < 0.02) was significantly more frequent in EBV-carrying gastric carcinomas. The latter involves loci, which have already been linked to gastric carcinogenesis such as the DCC and SMAD4 gene. In contrast, the losses on chromosome 4 and 11 do not yet harbor a gene related to gastric carcinogenesis. No significant correlation was found between DNA-ploidy and the EBV-status. A number of chromosomal aberrations were found at comparable frequencies in both groups, i.e., losses of chromosome 17, 12q, and loss of 1p. Interestingly, gains of 13q (10/34) and 3q (5/34) and loss of 1q (5/34) were solely observed in EBV-negative gastric carcinomas. Conclusions: These data indicate that EBV-carrying and EBV-negative gastric carcinomas have different pathogenetic pathways in which EBV might play a crucial role.

GASTROENTEROLOGY 2001;121:612-618

Section snippets

Clinical specimens

The identification of EBV-carrying gastric carcinomas was performed by EBER1/2-RNA in situ hybridization as described previously.6

Of 132 gastric adenocarcinomas, collected at the Department of Pathology of the University Hospital Vrije Universiteit, Amsterdam, the Netherlands, including 10 EBV-carrying gastric carcinomas, as has been published recently,6 CGH data had been obtained in 44 cases.15 None of the EBV-carrying gastric carcinomas used in this study were of the lymphoepithelioma-like

Chromosomal aberrations in EBV-carrying and EBV-negative gastric adenocarcinomas

The mean number of chromosomal losses in EBV-carrying gastric carcinomas was clearly higher than in EBV-negative gastric carcinomas (9.4 [range, 0–14] and 6.7 [range, 0–15] respectively) but this difference did not reach statistical significance. The mean of chromosomal events was also higher in EBV-carrying gastric carcinomas (12 vs. 10, not significant). In contrast, the mean number of chromosomal gains was lower in the EBV-carrying gastric carcinomas (2.6 vs. 3.3 [range, 0–13 each], not

Discussion

The present study is the first study to investigate genetic instability on the chromosomal level comparing EBV-carrying and EBV-negative gastric carcinomas using CGH analysis. Genetic instability on the chromosomal level is the major type of genetic instability in gastric cancer. The chromosomal changes detected by CGH analysis might point at specific chromosomal regions that might play a role in the pathogenesis of these carcinomas. We find chromosomal aberrations which are either restricted

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    Address requests for reprints to: Adriaan van den Brule, Ph.D., Department of Pathology, Molecular Pathology Section, University Hospital Vrije Universiteit, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. e-mail: [email protected]; fax: (31) 20 444 2964.

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