Integration of Epstein-Barr virus in Burkitt's lymphoma cells leads to a region of enhanced chromosome instability.
BACKGROUND
Several lymphomas are associated with Epstein-Barr virus (EBV) infection. However EBV is not detectable in 100% of cases using standard staining techniques. It still remains an open question whether in these EBV-negative cases EBV has never infected the cell, whether it has infected the cell and escapes conventional screening methods, or whether it has been lost again after initial infection.


METHODS
The physical status of EBV in the Burkitt's lymphoma cell line BL60-P7 as well as in three somatic cell hybrids between BL60-P7 and its autologous EBV-immortalized lymphoblastoid cell line IARC 277 was analyzed using conventional cytogenetics, Southern blotting, and fluorescence in situ hybridization (FISH).


RESULTS
Integration of EBV into the host genome of the lymphoma cell line BL60-P7 leads to an achromatic gap which causes a 'vulnerable site'. In hybrid cells, loss of integrated EBV, together with an adjacent chromosomal fragment, occurs during long-term cultivation. The integrated EBV genome, including genes encoding for LMP and EBER, is partly deleted.


CONCLUSIONS
We assume that integration of EBV into the host cell genome could be a more common event in lymphoma cells. Partially deleted EBV might escape standard detection assays. The integration might constitute a chromosomal region prone to break events akin to the phenomenon of fragile sites, leading to the loss of viral DNA as well as chromosomal DNA. This observation makes it tempting to speculate that under certain conditions EBV can act in lymphomagenesis by a so-called hit-and-run mechanism.
Jox
A
A
Department of Internal Medicine I, University of Cologne, Germany.
Rohen
C
C
Belge
G
G
Bartnitzke
S
S
Pawlita
M
M
Diehl
V
V
Bullerdiek
J
J
Wolf
J
J
D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000821:virology*; D002843:Chromatin / Q000235:genetics*; D002872:Chromosome Deletion; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D014407:Tumor Cells, Cultured
D002843:Chromatin