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This dissertation, BARF1 Sequence Analysis and Functional Significance in EBV-Related Disorders by Xuan, Liu, 劉絢, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled BARF1 Sequence Analysis and Functional Significance in EBV-Related Disorders Submitted by LIU Xuan For the degree of Master of Philosophy at the University of Hong Kong in August 2005 Nasopharyngeal carcinoma is a common malignancy in the Southern China region whilst it occurs with a low incidence in other parts of the world. Of the greater than 90 genes encoded by Epstein-Barr virus (EBV), BARF1 and LMP1 are two postulated oncogenes, because of their transformation and immortalization properties. In this study, the presence and sequence variation of EBV encoded BARF1 gene was investigated. BARF1 was detected in the peripheral blood of normal blood donors with a low incidence (about 10%) by PCR and ISH. Whilst BARF1 is able to increase Bcl-2 expression in cell lines, ISH and IHC investigations showed no effect of BARF1 on Bcl-2 expression in the nasopharyngeal carcinoma and gastric cancers. The BARF1 and LMP1 sequences of the NPCs from Hong Kong and North Africa were analyzed. 4 types of BARF1 amino acid sequences were detected in the Hong Kong NPCs, and wild type BARF1 (90%) and del-LMP1 (90.3%), which were supposed to have more oncogenetic properties, were more prevalent in Hong Kong NPCs. The incidence of the del-LMP1 appeared lower (50%) in the NPCs from North Africa, and all of the NPC cases (100%) from North Africa had the mutated BARF1 (codon-29: V→A) while the incidence of this mutation was much lower (8%) in Hong Kong NPCs. This polymorphism appeared to have no functional effect on growth rates of NPC cell lines. The transfection of BARF1 up-regulated Bcl-2 expression of the cell lines (by western blotting), but no increased cell growth rate and morphology change was detected. The results suggest that BARF1 might play a more important role in the early stages in epithelial oncogenesis. An abstract of 270 words DOI: 10.5353/th_b3619044 Subjects: OncogenesEpstein-Barr virus - GeneticsNasopharynx - Cancer - Genetic aspects

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