title: EBNA-1 gene sequences in Brazilian and American patients with Hodgkin's disease.
abstract: We examined the types of Epstein-Barr virus-associated nuclear antigen-1 (EBNA-1) gene carboxy (C)-terminal mutations occurring in Hodgkin's disease (HD) and reactive tissues from two different geographic regions. Previously reported EBNA-1 C-terminal region amino acid sequence variants, based on the amino acid at codon 487, include Prototype (P)-ala, which is found in the B95.8-derived prototype virus, P-thr, Variant (V)-leu, V-val, and V-pro. Using polymerase chain reaction (PCR) to amplify portions of the EBNA-1 gene, followed by DNA sequencing, we found a single EBNA-1 gene sequence variant in each tissue, whether reactive or neoplastic and whether from Brazil or the United States. Variant EBNA-1 gene sequences were more common in both neoplastic and non-neoplastic tissues from different geographic areas than the so-called prototype sequence. In the 17 Brazilian HD cases, 4 cases had P-thr variants and 13 had V-leu variants. In the six reactive tissues from Brazil, one had a P-ala variant, two had P-thr variants, and three had V-leu variants. In the 12 American HD cases, 2 had P-ala variants, 6 had P-thr variants, and 4 had V-leu variants. The 11 American reactive tissues included 2 P-ala variants, 5 P-thr variants, and 4 V-leu variants. In both countries, there were similar variant EBNA-1 sequences present in normal tissues and HD cases. Compared with the P-ala and P-thr cases, the V-leu cases were more likely to have the 30-bp latent membrane protein 1 (LMP1) gene deletion (P = 0.0075). In addition, cases of HD with the V-leu were statistically associated with a substitution of asparagine for glutamine at codon 322 of the C-terminal portion of the LMP1 gene. Our results suggest that any variation in EBNA-1 gene sequence is caused by a polymorphism present in pre-existing viral strains in the underlying population, and not a mutation occurring during oncogenesis.
authors.affiliation: Division of Pathology, City of Hope National Medical Center, Duarte, CA 91010-0269, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Chang
authors.forename: Y Y
authors.initials: YY
authors.lastname: Chen
authors.forename: W G
authors.initials: WG
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: C
authors.initials: C
authors.lastname: Bacchi
authors.forename: M
authors.initials: M
authors.lastname: Bacchi
authors.forename: L M
authors.initials: LM
authors.lastname: Weiss
mesh_terms: D001938:Brazil; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D017353:Gene Deletion; D005814:Genes, Viral; D006689:Hodgkin Disease / Q000235:genetics* / Q000821:virology; D006801:Humans; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014481:United States
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens