Epstein-Barr virus-associated nuclear antigen-1 carboxy-terminal gene sequences in Japanese and American patients with gastric carcinoma.

We examined Epstein-Barr virus (EBV)-associated nuclear antigen-1 (EBNA-1) gene carboxy (C)-terminal deletions occurring in gastric carcinoma and noncarcinoma tissues from two different ethnic populations. Previously reported EBNA-1 C-terminal region amino acid sequence variations include five subtypes based on the amino acid at codon 487: Prototype (P)-ala, which is found in the B95.8-derived prototype virus; P-thr; Variant (V)-pro; V-leu; and V-val. Using polymerase chain reaction to amplify fragments of the EBNA-1 gene, followed by gene sequencing, we identified a single EBNA-1 gene sequence variant (V-val') in all 25 cases of known EBV-positive gastric carcinoma and all 8 cases of known EBV-positive reactive follicular hyperplasia from Japan. All 17 cases of known EBV-positive American gastric carcinomas had a single EBNA-1 gene sequence, including 3 P-ala or P-ala variants, 9 P-thr, 4 V-leu or V-leu variants, and 1 V-val'. All 11 cases of American reactive lymphoid tissue also had a single EBNA-1 gene sequence, including 2 P-ala variants, 5 P-thr or P-thr variants, and 4 V-leu. Variant EBNA-1 sequences were more common in both carcinoma and non-neoplastic tissues than the prototype sequence, whether from Japan or America. The EBNA-1 gene sequences found in the two ethnic populations differed, suggesting that variation in EBNA-1 gene sequence is due to polymorphisms present within pre-existing viral strains prevalent within various ethnic populations. The EBNA-1 gene sequences in reactive tissues were similar to those in malignant tissues from the same ethnic population, suggesting that the differences in EBNA-1 gene sequences do not result from mutation occurring during neoplastic transformation and that there may not be a selective cell tropism for different EBNA-1 proteins, as previously suggested.