Genomic analysis of Epstein-Barr virus in nasal and peripheral T-cell lymphoma: a comparison with nasopharyngeal carcinoma in an endemic area.

Abstract

The Epstein-Barr virus (EBV) is prevalent in nasal and peripheral T-cell lymphoma (NPTL) in Taiwan, where nasopharyngeal carcinoma (NPC) is endemic. In order to understand the pathogenesis of these two malignancies in this endemic area, genomic analysis of EBV in NPTL with comparison 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 membrane 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 mononucleosis (IM) was simultaneously studied as representative of normal healthy carriers. Similar to NPC and IM, the EBV in NPTL was found to belong to the type A strain in the majority (18 of 19) of cases by analyzing the 3' divergence of EBNA-2 genes. The extra restriction enzyme site 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 previously characterized in Chinese NPC also prevailed in NPTL and IM with an identical nucleotide sequence. No correlation exists between the EBV subtype and its variants. In conclusion, type A EBV is prevalent in Taiwanese NPTL, a finding much distinct from the dominance of type B virus in nonendemic European patients. The EBV genomes in NPTL are closely similar to those in IM or normal healthy carriers, but are distinct 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-associated diseases. The rarity of the "f" variant in NPTL and its high frequency in NPC may explain the differential tumorigenesis of different EBV strains.