Distinct chromosomal aberrations in Epstein-Barr virus-carrying gastric carcinomas tested by comparative genomic hybridization.
OBJECTIVE
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.
zur Hausen
A
A
Department of Pathology, Section Molecular Pathology, University Hospital Vrije Universiteit, Amsterdam, the Netherlands.
van Grieken
N C
NC
Meijer
G A
GA
Hermsen
M A
MA
Bloemena
E
E
Meuwissen
S G
SG
Baak
J P
JP
Meijer
C J
CJ
Kuipers
E J
EJ
van den Brule
A J
AJ
D000230:Adenocarcinoma / Q000235:genetics* / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D013274:Stomach Neoplasms / Q000235:genetics* / Q000821:virology