GENOMIC ANALYSIS OF EPSTEIN-BARR-VIRUS IN NASAL AND PERIPHERAL T-CELLLYMPHOMA - A COMPARISON WITH NASOPHARYNGEAL CARCINOMA IN AN ENDEMIC AREA

The Epstein-Barr virus (EBV) is prevalent in nasal and peripheral T-ce ll lymphoma (NPTL) in Taiwan, where nasopharyngeal carcinoma (NPC) is endemic. In order to understand the pathogenesis of these two malignan cies in this endemic area, genomic analysis of EBV in NPTL with compar ison to NPC is important. We investigated the EBV subtype (types A and B), BamH-I ''f'' variant, and the Xho-I site mutant of the latent mem brane protein-1 (LMP-1) gene in 19 cases of EBV-associated NPTL and in 30 cases of NPC. EBV DNA from three patients with infectious mononucl eosis (IM) was simultaneously studied as representative of normal heal thy carriers. Similar to NPC and IM, the EBV in NPTL was found to belo ng to the type A strain in the majority (18 of 19) of cases by analyzi ng the 3' divergence of EBNA-2 genes. The extra restriction enzyme sit e in the BamHI-F region (''f'' variant] of EBV DNA was frequently (15 of 30) demonstrated in NPC, but only rarely (1 of 19) was it detected in NPTL and IM (0 of 3). The Xho-I site mutant of the LMP-1 gene previ ously characterized in Chinese NPC also prevailed in NPTL and IM with an identical nucleotide sequence. No correlation exists between the EB V subtype and its variants. In conclusion, type A EBV is prevalent in Taiwanese NPTL, a finding much distinct from the dominance of type B v irus in nonendemic European patients. The EBV genomes in NPTL are clos ely similar to those in IM or normal healthy carriers, but are distinc t from NPC for the infrequency of the ''f'' variant. The prevalence of the LMP-1 mutant in this endemic region suggests that this EBV strain may confer a growth advantage role in the pathogenesis of these EBV-a ssociated diseases. The rarity of the ''f'' variant in NPTL and its hi gh frequency in NPC may explain the differential tumorigenesis of diff erent EBV strains. (C) 1996 Wiley-Liss, Inc.