PMID- 10487851
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 155
IP  - 3
DP  - 1999 Sep
TI  - Epstein-Barr virus (EBV) nuclear antigen (EBNA)-4 mutation in EBV-associated 
      malignancies in three different populations.
PG  - 941-7
AB  - Different ethnic groups with a high human leukocyte antigen (HLA)-A11 prevalence 
      have been shown to experience a high rate of Epstein-Barr virus (EBV) infection, 
      EBV-associated malignancies, and Epstein-Barr nuclear antigen (EBNA)-4 mutations. 
      The epitopes 399-408 and 416-424 of EBNA-4 are major antigenic epitopes that 
      elicit an HLA-A11 cytotoxic T lymphocyte (CTL) response to EBV infection. 
      Mutations selectively involving one or more nucleotide residues in these epitopes 
      affect the antigenicity of EBNA-4, because the mutant EBV strains are not 
      recognized by the HLA-A11-restricted CTLs. To investigate these mutations in 
      common EBV-associated malignancies occurring in different populations, we studied 
      the mutation rate of epitopes 399-408 and 416-424 of EBNA-4 in 25 cases of 
      EBV-associated Hodgkin's disease (HD), nine cases of AIDS-related non-Hodgkin's 
      lymphoma, and 37 cases of EBV-associated gastric carcinoma (GC) from the United 
      States, Brazil, and Japan. We found one or more mutations in these two epitopes 
      in 50% (6/12) of United States HD, 15% (2/13) of Brazilian HD, 50% (6/12) United 
      States GC and 28% (7/25) Japanese GC, and 22% (2/9) of United States 
      AIDS-lymphoma. Similar mutations were found in 30% (3/10) of United States 
      reactive, 0% (0/6) of Brazilian reactive, and 25% (2/8) Japanese reactive 
      tissues. The most frequent amino acid substitutions were virtually identical to 
      those seen in previously reported isolates from EBV-associated nasopharyngeal 
      carcinomas and Burkitt's lymphomas occurring in high prevalence HLA-A11 regions. 
      However, only 2/28 (7%) mutations occurred in HLA-A11-positive patients. Our 
      studies suggest that: 1) EBNA-4 mutations are a common phenomenon in 
      EBV-associated HD, GC, and AIDS-lymphoma; 2) the mutation rate does not vary in 
      these geographic areas and ethnic groups; 3) EBNA-4 mutations in EBV-associated 
      United States and Brazilian HD, United States and Japanese GC, and United States 
      AIDS lymphomas are not related to patients' HLA-A11 status.
FAU - Chu, P G
AU  - Chu PG
AD  - Division of Pathology, City of Hope National Medical Center, Duarte, California 
      91010-0269, USA.
FAU - Chang, K L
AU  - Chang KL
FAU - Chen, W G
AU  - Chen WG
FAU - Chen, Y Y
AU  - Chen YY
FAU - Shibata, D
AU  - Shibata D
FAU - Hayashi, K
AU  - Hayashi K
FAU - Bacchi, C
AU  - Bacchi C
FAU - Bacchi, M
AU  - Bacchi M
FAU - Weiss, L M
AU  - Weiss LM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (DNA, Viral)
RN  - 0 (Epitopes)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A11 Antigen)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Base Sequence
MH  - Carcinoma/virology
MH  - DNA Mutational Analysis
MH  - DNA, Viral/analysis
MH  - Epitopes/genetics
MH  - Epstein-Barr Virus Nuclear Antigens/*genetics
MH  - HLA-A Antigens/genetics
MH  - HLA-A11 Antigen
MH  - Hodgkin Disease/*virology
MH  - Humans
MH  - Lymphoma, AIDS-Related/*virology
MH  - Lymphoma, Non-Hodgkin/*virology
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Polymerase Chain Reaction
MH  - Stomach Neoplasms/*virology
PMC - PMC1866909
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
PMCR- 2000/03/01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
PHST- 2000/03/01 00:00 [pmc-release]
AID - S0002-9440(10)65193-0 [pii]
AID - 1840 [pii]
AID - 10.1016/S0002-9440(10)65193-0 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Sep;155(3):941-7. doi: 10.1016/S0002-9440(10)65193-0.