Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches

Nasopharyngeal carcinoma (NPC) is consistently associated with EBV infection and prevalence in southern China and Southeast Asia. In addition to EBV, the development of NPC involves cumulative genetic and epigenetic changes influenced by predisposing genetic factors and environmental carcinogens. Over the past two decades, knowledge of genetic and epigenetic alterations of NPC has rapidly accumulated. Multiple chromosomal abnormalities (e.g copy number changes on chromosomes 3p, 9p, 11q, 12p, and 14q), gene alterations (e.g. p16 deletion and LTBR amplification), and epigenetic changes (e.g. RASSF1A and TSLC1 methylation) have been identified by various genome-wide approaches, such as allelotyping, CGH, and microarray analysis. In this review, we will discuss the critical genetic events that contribute to the initiation and progression of NPC. Studies on the precancerous lesions and in vitro immortalized nasopharyngeal epithelial cell models provide important evidence for the involvement of genetic alterations and EBV infection in early development of this cancer. A hypothetical model describing the role of EBV latent infection and multiple genetic changes in NPC tumorigenesis is proposed. (C) 2012 Elsevier Ltd. All rights reserved.