INTEGRATION OF EPSTEIN-BARR-VIRUS IN BURKITTS-LYMPHOMA CELLS LEADS TOA 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 s tandard 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, o r whether it has been lost again after initial infection. Materials an d methods: The physical status of EBV in the Burkitt's lymphoma cell l ine BL60-P7 as well as in three somatic cell hybrids between BL60-P7 a nd its autologous EBV-immortalized lymphoblastoid cell line IARC 277 w as analyzed using conventional cytogenetics, Southern blotting, and fl uorescence in situ hybridization (FISH). Results: Integration of EBV i nto the host genome of the lymphoma cell line BL60-P7 leads to an achr omatic 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 ge nes encoding for LMP and EBER, is partly deleted. Conclusion: We assum e that integration of EBV into the host cell genome could be a more co mmon event in lymphoma cells. Partially deleted EBV might escape stand ard detection assays. The integration might constitute a chromosomal r egion prone to break events akin to the phenomenon of fragile sites, l eading to the loss of viral DNA as well as chromosomal DNA. This obser vation makes it tempting to speculate that. under certain conditions E BV can act in lymphomagenesis by a so-called hit-and-run mechanism.