Epstein-Barr virus nuclear antigen (EBNA)-1 carboxy-terminal and EBNA-4 sequence polymorphisms in nasal natural killer/T-cell lymphoma in the United States.
Epstein-Barr virus (EBV) polymorphisms were examined in 12 cases of nasal natural killer (NK)/T-cell lymphoma diagnosed in the United States (U.S.-NL) with respect to the EBV-associated nuclear antigen (EBNA)-1 carboxy (C)-terminal region and the EBNA-4 region. A single dominant EBV strain was found in all cases. EBNA-1 sequences were remarkably homogeneous, showing either a P-ala (2/12) or P-ala variant (9/12) sequence. Other EBNA-1 subtypes known to be common in U.S.-reactive samples, such as P-thr or V-leu, were not identified. The final case had a base deletion with frame shift and premature stop codon. EBNA-1 C-terminal amino acid substitutions were common at codons 499 (10/12 cases), 502 (7/12), 524 (9/12), and 528 (6/12), all previously reported "hot spots." However, unlike previous reports of other EBV-associated neoplastic and reactive tissues, mutations were absent at residues 487 and 492. Mutations within HLA-A11-restricted immunogenic EBNA-4 epitopes 399-408 and 416-424 occurred in 3 of 12 cases but were not associated with HLA-A11 status. In summary, the exclusive finding of P-ala variant or P-ala EBNA-1 sequences in U.S.-NL cases differs from that reported in U.S.-reactive and non-U.S.-NL cases. Although the significance of this difference is not known for certain, it may be related to geographic and/or site-specific variations, rather than oncogenicity per se.
Gaal
Karl
K
Division of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA. kgaal@coh.org
Weiss
Lawrence M
LM
Chen
Wen-Gang
WG
Chen
Yuan-Yuan
YY
Arber
Daniel A
DA
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007694:Killer Cells, Natural / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000821:virology; D009669:Nose Neoplasms / Q000235:genetics* / Q000821:virology; D011110:Polymorphism, Genetic; D044469:Racial Groups; D013601:T-Lymphocytes / Q000821:virology*; D014481:United States
C438197:EBNA4 antigen; D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1