Gene analysis of Epstein-Barr virus-associated lymphomas in Hu-Pbl/SCID chimeras.

Abstract

AIMS AND BACKGROUND:

The mechanisms of Epstein-Barr virus (EBV)-associated tumor development are incompletely understood. The aim of this study was to investigate the gene expression of EBV-associated lymphomas in hu-PBL/SCID mice.

METHODS:

Human peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were transplanted into severe combined immunodeficiency (SCID) mice. In situ hybridization was used to detect EBV-encoded small RNA- 1 (EBER1) in tumor tissues. Mutation of TP53 exons 5-8 in EBV-induced lymphomas was analyzed by PCR-SSCP. Immunohistochemical staining was used to examine EBV gene products and cellular oncoproteins.

RESULTS:

Twenty-one of 29 mice developed tumors. EBER1 was positive in the nuclei of almost all tumor cells. Immunohistochemistry showed positive staining of LMP1, EBNA2 and ZEBRA in a small number of tumor cells. Immunohistochemically detectable p53 protein expression was common (85.7%), but TP53 gene mutations were identified in only four cases (19.1%) of EBV-associated lymphomas. Positivity rates of C-myc, Bcl-2 and Bax expression were 100%, 95.2%, and 90.5%, respectively, in the 21 cases of EBV-associated lymphomas.

CONCLUSIONS:

Our preliminary findings suggest that EBV-associated lymphomas in hu-PBL/SCID chimeras show EBV infection, expression of oncogenic viral genes, and overexpression of cellular oncogenes. TP53 gene mutations are rare but p53 protein is commonly expressed in EBV-associated lymphomas.

• Authors: Runliang Gan, Xiaoli Xie, Jie He, Xiaomin Liu, Li Hong, Yunlian Tang, Fang Liu, Hailong Xie
• Journal: Tumori (Tumori) 2010 May-Jun Vol. 96 Issue 3 Pg. 465-72 ISSN: 0300-8916 [Print] United States
• PMID: 20845810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• Carcinogens
• MYC protein, human
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-myc
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein

Topics

• Animals
• Carcinogens
• Chimera
• Epstein-Barr Virus Infections (complications)
• Gene Expression Regulation, Neoplastic
• Herpesvirus 4, Human (genetics, isolation & purification)
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Lymphocytes
• Lymphoma (genetics, pathology, virology)
• Mice
• Mice, SCID
• Polymerase Chain Reaction
• Polymorphism, Single-Stranded Conformational
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Proto-Oncogene Proteins c-myc (genetics)
• Tumor Suppressor Protein p53 (genetics)
• Up-Regulation
• bcl-2-Associated X Protein (genetics)