The nucleotide polymorphisms within the Epstein-Barr virus C and Q promoters from nasopharyngeal carcinoma affect transcriptional activity in vitro.

Abstract

Epstein-Barr virus (EBV) is a ubiquitous human gamma herpesvirus that is associated with Burkitt's lymphoma (BL), gastric carcinoma, nasopharyngeal carcinoma (NPC), and NK/T-cell lymphoma. Two viral promoters, Cp and Qp, are important for EBV latent infection. The latency Cp, which is used in primary infection, drives expression of the full spectrum of EBV nuclear antigens. Qp is active in EBV-associated tumors and drives the latency I/II expression pattern. In this study, we determined nucleotides polymorphisms in the Cp and Qp promoter regions in peripheral blood mononuclear cells (PBMCs) from Cantonese healthy carriers and in biopsies of NPC, nasal NK/T lymphoma, BL, and gastric carcinoma. The sequence changes of -12G>T and +69 C>T in Cp and -197 G>A and +1 G>C in Qp were frequently identified in NPC. Transient transfection studies using luciferase gene reporters revealed a significant reduction (57.11%) in gene expression from the Cp +69T variant and increased expression (43.5%) from the Qp +1C variant compared to the prototype, suggesting that these sequence variations affect promoter activity. Our results indicate that the nucleotides polymorphisms in Cp and Qp occur frequently in NPC and might contribute to the oncogenesis of EBV.

• Authors: Feng-Wei Wang, Xian-Rui Wu, Wen-Ju Liu, Ying-Jie Liang, Yu-Fan Huang, Yi-Ji Liao, Chun-Kui Shao, Yong-Sheng Zong, Shi-Juan Mai, Dan Xie
• Journal: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery (Eur Arch Otorhinolaryngol) Vol. 269 Issue 3 Pg. 931-8 (Mar 2012) ISSN: 1434-4726 [Electronic] Germany
• PMID: 22146864 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• Epstein-Barr Virus Nuclear Antigens

Topics

• Carcinoma
• DNA, Viral (genetics)
• Epstein-Barr Virus Nuclear Antigens (biosynthesis, genetics)
• Gene Expression Regulation, Viral
• Herpesvirus 4, Human (genetics, metabolism)
• Humans
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (genetics, pathology, virology)
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic (genetics)
• Transcription, Genetic
• Transcriptional Activation (genetics)
• Tumor Cells, Cultured