EPSTEIN-BARR-VIRUS (EBV) IN ENDEMIC BURKITTS-LYMPHOMA - MOLECULAR ANALYSIS OF PRIMARY TUMOR-TISSUE

Many aspects of Epstein-Barr virus (EBV) and tumor biology have been s tudied in Burkitt's lymphoma (BL)-derived cell lines, However, in tiss ue culture, patterns of gene expression and C promoter-G (CpG) methyla tion often change and viral strain selection may occur. In this report , 10 cases of snap-frozen endemic BL tumors are characterized in terms of viral gene expression, promoter usage, methylation, and viral stra in. EBNA1 and BamHI-A rightward transcripts (BART) were detected in 7 of 7 and LMP2A transcripts in 5 of 7 tumors with well-preserved RNA. T ranscripts for the other EBNAs and for LMP1 were not detected in any t umor. These tumors differ from BL cell lines in that they lack a varie ty of lytic cycle transcripts. This pattern of viral gene expression i n endemic BL is similar to that reported in peripheral blood mononucle ar cells (PBMCs) from healthy EBV-seropositive individuals. EBNA1 tran scripts originated from the Q promoter (Qp) but not C, W, or F promote rs that drive transcription of EBNA1 in other circumstances. Whereas C p has been previously shown to be entirely CpG methylated in BL, bisul fite genomic sequencing showed virtually no methylation in Qp. Type-A EBV was detected in 6 of 10 and type B in 4 of 10 cases. A previously reported 30bp deletion variant in the carboxyl terminal of LMP1 gene w as detected in 5 of 10 cases. The association with both A and B strain s contrasts with EBV-associated Hodgkin's disease, nasopharyngeal carc inoma, and post-transplant lymphoproliferative disease, which are much more consistently associated with A strain virus. (C) 1998 by The Ame rican Society of Hematology.