A shared gene expression signature in mouse models of EBV-associated and non-EBV-associated Burkitt lymphoma.
The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional profiles of tumor cells from LMP2A/λ-MYC and λ-MYC mice are strikingly similar, with fewer than 20 genes differentially expressed. We evaluated the functional significance of one of the most interesting differentially expressed genes, Egr1, and found that it was not required for acceleration of tumor onset by LMP2A. Our studies demonstrate the remarkable ability of LMP2A to affect the pretumor B-cell phenotype and tumorigenesis without substantially altering gene expression in tumor cells.
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Kathryn T
KT
Bieging
Kamonwan
K
Fish
Subbarao
S
Bondada
Richard
R
Longnecker
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016259:Genes, myc / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D051917:Leukosialin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014763:Viral Matrix Proteins / Q000235:genetics
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D051917:Leukosialin; D014763:Viral Matrix Proteins; D017493:Leukocyte Common Antigens