[Expression of Epstein-Barr virus genes in EBV-associated gastric carcinoma]

Abstract

Background & objective: Epstein-Barr virus (EBV) is associated with the development of many malignant tumors. The forms of EBV and the expression of EBV genes in Burkitt's lymphoma and nasopharyngeal carcinoma (NPC) have been reported. These studies showed that the forms of EBV and the expression of EBV genes are various in different types of malignancies. However, there were only a few reports about the expression of EBV genes, especially the lytic genes, in gastric carcinoma tissues. This study was to determine the expression of EBV latent and lytic infection genes in gastric carcinoma at the transcriptional level by RT-PCR and Southern hybridization,and investigate the relationship between EBV-encoded genes and the tumorigenesis of gastric carcinoma at the molecular level.

Methods: One hundred and eighty-five gastric carcinoma and corresponding para-carcinoma tissues were tested for EBV genome by polymerase chain reaction (PCR)-Southern analysis. EBV-encoded small RNA 1 (EBER1) of the PCR positive specimens was determined by in situ hybridization (ISH). Gastric carcinoma with positive EBER1 signals was confirmed EBV- associated gastric carcinoma (EBVaGC). RT-PCR and Southern hybridization were used to determine the expression of nuclear antigen (EBNA) promoters (Qp, Wp and Cp), EBNA 1 and 2,latent membrane protein (LMP) 1, 2A, and 2B and lytic genes (immediate-early genes BZLF1 and BRLF1, early genes BARF1 and BHRF1, late genes BcLF1 and BLLF1) in EBVaGCs.

Results: There were 13 EBV positive samples in gastric carcinomas (7.03%), but no EBV positive sample in corresponding para-carcinomas. The transcripts of Qp were detected in all of the 13 EBVaGCs tissues, while both Wp and Cp were silent. All of the 13 cases expressed EBNA1 mRNA, but no EBNA2, LMP1, and LMP2B mRNA. LMP2A mRNA was detected in 5 of the 13 cases. Of the 13 EBVaGCs, 7 exhibited BcLF1 transcript and 2 exhibited BHRF1 transcript. The transcripts of BZLF1 were detected in 6 cases, and those of BARF1 also in 6 cases. No BLLF1 and BRLF mRNA were detected in the 13 EBVaGCs.

Conclusions: The latent pattern of EBV in EBVaGCs corresponds to the latency I or unique latency I/II, intermediate between the latency I and II. Part of lytic infection genes are expressed in EBVaGCs tissues. BARF1 and BHRF1 genes express in part of gastric carcinomas and their roles in gastric tumorigenesis need to be further studied.