Unique transcription pattern of Epstein-Barr Virus (EBV) in EBV-carrying gastric adenocarcinomas : Expression of the transforming BARF1 gene

Approximately 10% of gastric adenocarcinomas worldwide are associated with human EBV. These carcinomas generally do not express the latent membrane protein 1 (LMP1), the major known EBV oncogene. Recently, another EBV gene [ie., BARF1 (BamHI A rightward open reading frame)] was shown to have transfo...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-05, Vol.60 (10), p.2745-2748
Main Authors: HAUSEN, A. Z, BRINK, A. A. T. P, CRAANEN, M. E, MIDDELDORP, J. M, MEIJER, C. J. L. M, VAN DEN BRULE, A. J. C
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - virology
BARF0 gene
BARF1 gene
Biological and medical sciences
Cell Transformation, Neoplastic - genetics
Epstein-Barr virus
Gastroenterology. Liver. Pancreas. Abdomen
Herpesviridae Infections - genetics
Herpesvirus 4, Human - genetics
Humans
In Situ Hybridization
LMP2A gene
Medical sciences
Q/K-A gene
Stomach Neoplasms - genetics
Stomach Neoplasms - virology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Transcription, Genetic
Tumor Virus Infections - genetics
Tumors
Viral Proteins - biosynthesis
Viral Proteins - genetics
Virus Latency
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Summary:Approximately 10% of gastric adenocarcinomas worldwide are associated with human EBV. These carcinomas generally do not express the latent membrane protein 1 (LMP1), the major known EBV oncogene. Recently, another EBV gene [ie., BARF1 (BamHI A rightward open reading frame)] was shown to have transforming and immortalizing capacities. Therefore, in this study, we investigated the expression of BARF1 in EBV-carrying gastric adenocarcinomas in relation to the expression of other latent EBV transcripts. In the present study, 10 of 132 gastric adenocarcinomas tested positive for EBV using EBER1/2-RNA in situ hybridization. We demonstrate BARF1 gene transcription in nine EBV-carrying gastric adenocarcinomas (with sufficient RNA quality) using the BARF1-specific nucleic acid sequence-based amplification assay. In addition, we also detected other latent EBV transcripts (ie., BARF0-, LMP2A-, and Q/K-driven EBNA1 transcripts in these carcinomas using reverse transcription-PCR analysis. No expression of LMP1, EBNA2, and ZEBRA (either at transcription or protein level) was found. In addition, two cases were positive for BHRF1 transcripts, the viral bcl-2 homologue. Thus, together with BARF1 transcription, a unique and distinct EBV latency type has been found in EBV-associated gastric adenocarcinomas. Because BARF1 exerts immortalizing effects on human epithelial cells in vitro and EBV-carrying gastric adenocarcinomas lack the expression of LMP1, the BARF1 gene might act as the viral oncogene in EBV-carrying gastric carcinomas. The BARF1 gene offers an alternative way for EBV-mediated oncogenesis other than LMP1.
ISSN:0008-5472
1538-7445