title: 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.affiliation: The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou, 510060, China.
authors.forename: Feng-Wei
authors.initials: FW
authors.lastname: Wang
authors.forename: Xian-Rui
authors.initials: XR
authors.lastname: Wu
authors.forename: Wen-Ju
authors.initials: WJ
authors.lastname: Liu
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Liang
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Huang
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.forename: Chun-Kui
authors.initials: CK
authors.lastname: Shao
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Zong
authors.forename: Shi-Juan
authors.initials: SJ
authors.lastname: Mai
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D002277:Carcinoma; D004279:DNA, Viral / Q000235:genetics*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens