Gene analysis of Epstein-Barr virus-associated lymphomas in Hu-Pbl/SCID chimeras.
OBJECTIVE
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.
Gan
Runliang
R
Cancer Research Institute, University of South China, Hengyang City, China. gan998@yahoo.com
Xie
Xiaoli
X
He
Jie
J
Liu
Xiaomin
X
Hong
Li
L
Tang
Yunlian
Y
Liu
Fang
F
Xie
Hailong
H
D000818:Animals; D002273:Carcinogens; D002678:Chimera; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008214:Lymphocytes; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics
C494826:BAX protein, human; D002273:Carcinogens; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein