Epstein-Barr virus and nasopharyngeal carcinoma

Lawrence S Young, Christopher W Dawson, Lawrence S Young, Christopher W Dawson

Abstract

Since its discovery 50 years ago, Epstein-Barr virus (EBV) has been linked to the development of cancers originating from both lymphoid and epithelial cells. Approximately 95% of the world's population sustains an asymptomatic, life-long infection with EBV. The virus persists in the memory B-cell pool of normal healthy individuals, and any disruption of this interaction results in virus-associated B-cell tumors. The association of EBV with epithelial cell tumors, specifically nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma (EBV-GC), is less clear and is currently thought to be caused by the aberrant establishment of virus latency in epithelial cells that display premalignant genetic changes. Although the precise role of EBV in the carcinogenic process is currently poorly understood, the presence of the virus in all tumor cells provides opportunities for developing novel therapeutic and diagnostic approaches. The study of EBV and its role in carcinomas continues to provide insight into the carcinogenic process that is relevant to a broader understanding of tumor pathogenesis and to the development of targeted cancer therapies.

Figures

Figure 1.. Epstein-Barr virus (EBV) latent gene…
Figure 1.. Epstein-Barr virus (EBV) latent gene expression in nasopharyngeal carcinoma (NPC).
In situ hydridization to the abundant EBV-encoded small RNAs (EBER) transcripts (left, upper panel) is the standard approach to detect EBV infection in cells and tissues. Immunohistochemical staining of NPC confirms EBNA1 expression in every tumor cell (right, upper panel). The expression of latent membrane protein 1 (LMP1) and LMP2A in NPC biopsies (lower panels) is more variable. The prominent lymphoid infiltrate in NPC is believed to contribute to the growth and survival of the tumor cells. (magnification, × 200)
Figure 2.. Schematic representation of NPC pathogenesis.
Figure 2.. Schematic representation of NPC pathogenesis.
This model proposes that loss of heterozygosity (LOH) occurs early in NPC pathogenesis, possibly as a result of exposure to environmental cofactors such as dietary components (e.g., salted fish). This results in low-grade, preinvasive lesions that, after additional genetic and epigenetic events, become susceptible to stable EBV infection. Once cells have become infected, EBV latent genes provide growth and survival benefits, resulting in the development of NPC. Additional genetic and epigenetic changes occur after EBV infection.

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