CHARACTERIZATION OF EPSTEIN-BARR VIRUS GENOMES IN TRANSPLANT LYMPHOMA/LYMPHOPROLIFERATIVE DISEASE

Abstract

Epstein-Barr Virus (EBV)-related lymphomas (L) and B cell lymphoproliferative diseases (LPD) are recognized with increasing frequency in pts after organ and mismatched allogeneic bone marrow transplantation (BMT). The high incidence may be due to the profound immune suppression, multiple copies or unique characteristics of the viral DNA. We investigated tumor UNA from 8 pts with L or LPD post-BMT and 1 post-renal transplantation for EBV clonality and rearrangement of viral EBV DNA. Tumor tissue from all pts contained multiple (8-50) copies of EBV DNA as detected by probing Southern blots with radioactive EBV probes. To determine whether the EBV DNA was in a circular or linear configuration, we probed the blots of BamHI-digested pt DNAs with a Bam NJ het fragment. The NJ het region is highly variable, thus a single band suggests a clonal proliferation of the virus. The samples with 2 or more bands represent either oligoclonal virus or linear EBV in tumor tissue. 6/9 pt DNAs had a single band suggesting presence of circular EBV DNA. 2/9 had 2 bands of different sizes that may represent linear DNA or different virus strains. One pt had evidence of circular and linear DNA, or possible multiple strains of EBV since 3 bands of viral DNA were seen with the NJ het probe. Since 7/9 pts had single bands (suggesting circular, clonal EBV DNA when probed with NJ Het) this may indicate that the circular DNA is transcribing viral genes important in initiating or maintaining the LPD and L.

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