CLONALITY, EXPRESSION AND METHYLATION PATTERNS OF THE EPSTEIN-BARR-VIRUS GENOMES IN LETHAL MIDLINE GRANULOMAS CLASSIFIED AS PERIPHERAL ANGIOCENTRIC T-CELL LYMPHOMAS

We analysed the terminal repeats of Epstein-Barr virus (EBV) in DNAs i solated from six lethal midline granuloma (LMG) biopsies. A single fus ed terminal fragment could be detected in each case, indicating that t hese angiocentric peripheral T cell lymphomas represent clonal prolife rations of cells infected with EBV on a single occasion. Using reverse transcriptase-PCR, we detected EBV nuclear antigen (EBNA) 1 and laten t membrane protein (LMP) 1, but not EBNA 2 messages in LMG biopsy RNAs . The splicing pattern of the EBNA 1 message was consistent with the u sage of a promoter localized in the BamHI F fragment (F promoter). The BamHI W fragment repeats and LMP-coding sequences were highly methyla ted in ah cases. In contrast, the LMP regulatory sequences were found to be hypomethylated or partially methylated, as in LMP-expressing nas opharyngeal carcinomas.