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

Abstract

SUMMARY: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. (Lab Invest 2002, 82:957-962).

Primary lymphoma arising in the nasal cavity among Japanese

“…Nasal lymphoma, though rare in western countries, is prevalent in Asian countries including Japan 1–3 . This lymphoma has been categorized as an extranodal natural killer (NK)/T‐cell lymphoma, nasal type in the new World Health Organization lymphoma classification 4 .…”

“…However, because of its relatively low incidence, the precise character of nasal lymphoma has not yet been fully elucidated. This lymphoma was classified as an NK/T‐cell type due to the uncertainty of its true NK cell origin 1–4 . In addition, there have been some reports indicating that certain lymphomas arising in the nasal cavity are of T‐ or B‐cell type 5–8 .…”

“…Nasal lymphoma, though rare in western countries, is prevalent in Asian countries including Japan. [1][2][3] This lymphoma has been categorized as an extranodal natural killer (NK) ⁄ T-cell lymphoma, nasal type in the new World Health Organization lymphoma classification. 4 However, because of its relatively low incidence, the precise character of nasal lymphoma has not yet been fully elucidated.…”

A Case of Epstein-Barr Virus (EBV)-Associated Thymic Carcinoid and Investigation of Existence of EBV-Infected Cells in Thymus and Thymic Tumors

“…Evidence supporting the presence of the EBV genome in NK or T lymphocytes has been reported previously (1,11,23,28). Regarding our case, we thus hypothesize that the thymic carcinoid tumor may have arisen in a peculiar microenvironment, such as proliferation of EBV-infected NK or T lymphocytes or immature cells.…”

Angiocentric Lesions of the Head and Neck

“…9 and 10). Although clonality cannot be detected by TCR studies, the detection of single circularized episome form of EBV in the neoplasm and or molecular demonstration of X chromosome inactivation in female patients with NK cell lymphoma provides evidence for clonal restriction [73][74][75]. Fig.…”