EBV infection is associated with human malignancies. Among all EBVassociated epithelial malignancies, the association between EBV infection and nasopharyngeal carcinoma is the strongest. NPC is a common cancer in Southeast Asia, particularly in southern regions of China including Hong Kong. The incidence of NPC in ethnic Chinese living in southern China, including Hong Kong, is ranging 50 to 100 folds higher than non-Chinese populations in North America and Europe. In undifferentiated NPC, which is the typical histopathological type of NPC in southern China, EBV could be detected in most, if not all, NPC cells. EBV infection has been postulated to be a crucial etiological factor in NPC pathogenesis, yet the underlying oncogenic mechanisms of EBV in NPC remain elusive. Deletions in chromosomes 3p and 9p could be detected in dysplastic lesions and histologically normal nasopharyngeal epithelium of southern Chinese prior to EBV infection. This leads to the hypothesis that genetically altered premalignant nasopharyngeal epithelial cells support EBV infection, and expansion of a specific EBV-infected clone of premalignant nasopharyngeal epithelial cells with the expression of lytic and latent genes of EBV drives further genomic instability in the EBV-infected nasopharyngeal epithelial cells, eventually leading to tumorigenic transformation. Latent membrane protein 1 is a well-documented EBV-encoded oncogene. LMP1 expression resulted in tumorigenic transformation of rodent fibroblast cells. Transgenic mice expressing LMP1 developed B cell lymphoma. LMP1 is commonly expressed in Hodgkin’s lymphoma and nasal lymphoma. LMP1 expression could be detected in preinvasive NPC lesions infected with EBV. LMP1 expression facilitates immortalization of nasopharyngeal epithelial cells by telomerase. All these Wortmannin observations support an important role of LMP1 in the early pathogenesis of NPC. Furthermore, LMP1 modulates multiple cell signaling pathways through activation of nuclear factor-kappa-B, Janusactivated kinase/signal transducer and activator of transcription, mitogen-activated protein kinase, protein kinase B and other signaling pathways to induce survival, anti-apoptosis and invasive properties in EBV-infected cells. The G2 checkpoint is essential for cell survival and maintenance of genomic stability. It delays cell cycle progression from G2 to M phase to provide time for correction of DNA damage or replication errors. Defective G2 checkpoint allows cells that carry chromosome aberrations to exit G2 and enter mitosis, leading to genomic instability which facilitates carcinogenesis. The impact of LMP1 on G2 checkpoint in nasopharyngeal epithelial cells has not been previously examined. In this study, we found that LMP1 impaired G2 checkpoint in nasopharyngeal epithelial cells, leading to formation of unrepaired chromatid-type aberrations in metaphase cells. We further found that defective Chk1 activation was responsible for the induction of defect in G2 checkpoint in LMP1- expressing nasopharyngeal epithelial cells.