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Variations of Epstein-Barr virus nuclear antigen 1 in Epstein-Barr virus-associated gastric carcinomas from Guangzhou, southern China.

Abstract
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the only viral protein consistently expressed in all EBV-associated malignancies, and play a critical role in the onset, progression, and/or maintenance of these tumors. Based on the signature changes at amino acid residue 487, EBNA1 is classified into five distinct subtypes: P-ala, P-thr, V-leu, V-val and V-pro. In the present study, the sequence variations of EBNA1 in EBV-associated gastric carcinoma (EBVaGC) and throat washing (TW) samples of healthy EBV carriers in Guangzhou, southern China, where nasopharyngeal carcinoma (NPC) is endemic, were analyzed by PCR and DNA sequencing. V-val subtype was the most predominant (53.6%, 15/28) in EBVaGC, followed by P-ala (42.9%, 12/28) and V-leu (32.1%, 9/28) subtypes. In TWs of healthy EBV carriers, V-val subtype was also predominant (85.7%, 18/21). The sequence variations of EBNA1 in EBVaGC were similar to those in TW of healthy EBV carriers (p>0.05), suggesting that the EBV strains in EBVaGC might originate from the viral strains prevalent within the background population. The predominance of V-val subtype in EBVaGC in Guangzhou was similar to that in EBVaGC in northern China and Japan, but was different from that in EBVaGC in America, suggesting that the variations of EBNA1 in EBVaGC represent geographic-associated polymorphisms rather than tumor-specific mutations. In addition, the EBNA1 variations in EBVaGC in gastric remnant carcinoma were also determined. V-leu subtype was detected in all 4 (100%) cases, although 2 cases occurred as mixed infection with P-ala subtype. This is different from the predominant V-val subtype in EBVaGC in conventional gastric carcinoma, suggesting that V-leu might be a subtype that adapts particularly well to the microenvironment within the gastric stump and enters the remnant gastric mucosa epithelia easily. This, to our best knowledge, is the first investigation of EBNA1 polymorphisms in EBVaGC from endemic area of NPC.
AuthorsJian-ning Chen, Na-na Zhang, Ye Jiang, Da-yang Hui, Zi-jin Wen, Hai-gang Li, Yun-gang Ding, Hong Du, Chun-kui Shao
JournalPloS one (PLoS One) Vol. 7 Issue 11 Pg. e50084 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID23189182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • EBV-encoded nuclear antigen 1
  • Epstein-Barr Virus Nuclear Antigens
Topics
  • Adult
  • Aged
  • Amino Acid Substitution
  • Base Sequence
  • Carcinoma (pathology, virology)
  • China
  • Epstein-Barr Virus Nuclear Antigens (genetics, metabolism)
  • Female
  • Gene Expression
  • Genetic Variation
  • Genotype
  • Herpesvirus 4, Human (genetics)
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Nasopharyngeal Neoplasms (pathology, virology)
  • Neoplasm Staging
  • Polymorphism, Genetic
  • Sequence Alignment
  • Stomach Neoplasms (pathology, virology)
  • Young Adult

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