Differences in EBNA2 and LMP-1 carboxy terminal region sequences of Epstein-Barr virus type a between the tumors in a multiple cancer patient

Using PCR, type A Epstein-Barr virus (EBV) infection was demonstrated in a squamous cell carcinoma of the maxilla (in a 52-year-old man) and the tongu e of the same patient 18 years later (at the age of 70). Furthermore, at th e age of 72, this patient developed an EBV-infected anaplastic large cell l ymphoma. Analysis of the terminal regions of the EBV genome revealed a mono clonal proliferation of EBV-infected lymphoma cells. However, sequence anal ysis of the EBV revealed a slight difference in the EBNA2 regions between t he virus-infected lymphoma and the squamous cell carcinomas. The mutations at 48991 (G -->T) and 48998 (C -->A) were demonstrated in the lymphoma. Alt hough the squamous cell carcinoma of the tongue occurred after an interval of is years, the mutation site in the carcinomas was the same, 49137 (A --> G), as compared with B95-8 strain EBV EBNA2. The mutations at 48991 and at 49137 were associated with amino acid changes, Arg --> Met and Thr --> Ala, respectively, but the alteration at 48998 was a silent mutation. Thirty-bp deletion in the LMP-1 carboxy terminal region was demonstrated in the viru s-infected lymphoma, but not in the squamous cell carcinomas. On the other hand, HTLV-1 proviral DNA (tax, gag and env) was not detected in the lymphoma, nor was HPV demonstrated in the squamous cell carcinomas, although Okinawa is known as an HTLV-1 and HPV prevalence region. The T-cel l receptor beta gene rearrangement was demonstrated in the lymphoma, but th e t(2;5) fusion transcript was not detected using PCR. Cytogenetic analysis of the lymphoma cells showed a complex hypertriploid karyotype with 76XY. The type A EBV infection might play a role in the carcinogenesis of the tum ors of our patient. Interestingly, the infected virus genome sequences, the EBNA2 and LMP-1 regions, which were closely associated with carcinogenesis in the squamous cell carcinomas and the lymphoma, showed slight difference s.