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[Cancer Research 60, 2745-2748, May 15, 2000]
© 2000 American Association for Cancer Research


Virology

Unique Transcription Pattern of Epstein-Barr Virus (EBV) in EBV-carrying Gastric Adenocarcinomas: Expression of the Transforming BARF1 Gene1

Axel zur Hausen, Antoinette A. T. P. Brink, Mikael E. Craanen, Jaap M. Middeldorp, Chris J. L. M. Meijer and Adriaan J. C. van den Brule2

Department of Pathology, Section Molecular Pathology [A. z. H., A. A. T. P. B, J. M. M., C. J. L. M. M., A. J. C. v. d. B.], and Department of Gastroenterology [M. E. C.], University Hospital Vrije Universiteit, 1007 MB Amsterdam, the Netherlands

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 [i.e., 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 (i.e., 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.




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