Integration of Epstein-Barr virus into the host genome: a potential risk factor for the development of malignant lymphoma.

A. Staratschek-Jox MD a, J. Bullerdiek PhD b, J. Wolf MD a

a Department of Internal Medicine I, University of Cologne, Germany. b Center for Human Genetics, University of Bremen, Germany

AIM Latent EBV infection in B-lymphocytes can be detected in about 95% of healthy adults. Although the expression of some EBV derived latent genes is linked to malignant transformation the occurrence of malignant lymphoma is a rare event. However, it is currently unknown which secondary events are necessary to establish the malignant phenotype of EBV positive lymphoma cells. 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 (LCL) IARC 277 was analyzed using conventional cytogenetics, Southern blotting, and fluorescence in situ hybridization. RESULTS We detected integration of EBV into the host genome of the lymphoma cell line BL60-P7 thereby leading to an achromatic gap causing a 'vulnerable site'. In hybrid cells, loss of integrated EBV DNA derived from BL60-P7, together with an adjacent chromosomal fragment, occurs during long-term cultivation while the LCL derived episomal EBV copies were retained. CONCLUSIONS Our data suggest that integration of EBV into the host cell genome is possibly a common event in EBV positive cells. The integration might constitute a chromosomal region prone to break events, leading to the loss of viral DNA as well as chromosomal DNA. These data form the platform for further studies to understand whether people carrying integrated EBV genomes in latently infected B-lymphocytes are of higher risk to develop malignant lymphoma.

KEY WORDS: Epstein-Barr virus, integration, lymphoma, risk factor.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment, Part 1.