Burkitt’s lymphomaand ebv – the role of LMP2A

One of the most interesting aspects of the gamma-herpesvirus Epstein-Barr virus (EBV) was the discovery of the virus and its association with human cancer. It was the first such virus identified with a known role in a human cancer despite animal studies in the early 1900s showing that viruses may be factor in cancer. The discovery of EBV began in 1957 when an Irish physician, Denis Burkitt, pursuing a medical career in Kampala, Uganda saw a young boy with swelling of both sides of his jaws that proved to be a lymphoma.1,2 The lymphoma was the most common cancer in African children and was fatal upon spread to other parts of the body. Burkitt became fascinated with the tumor that led him to carefully examine hospital medical records throughout Africa and embark on what he called his long safari documenting the incidence of the lymphoma. Burkitt found a definitive pattern of distribution of the tumor following the closely the incidence of malaria suggesting that a transmissible infectious agent was involved.3 The next key to the puzzle was work done by Anthony Epstein and Yvonne Barr in London. Anthony Epstein attended a lecture by Burkitt at Middlesex Hospital in London in 1961. They immediately began a collaboration with biopsies sent from Uganda, but it was not until 1964 that herpesvirus-like particles were observed in cells that Burkitt sent.4 Two other discoveries were also important in regard to understanding EBV disease in humans and its relationship to human cancers. First, the chance discovery that EBV was the etiological agent responsible for infectious mononucleosis by Warner and Gertrude Henle in 1967 and the characterization of the MYC chromosomal translocation in Burkitt lymphoma. This discovery in 1982 that the chromosomal abnormality found in all Burkitt lymphoma cells is independent of EBV status began to lay the foundation for understanding how viruses can contribute to human cancer. EBV has also been implicated in a variety of other cancers including Hodgkin’s lymphoma, nasopharyngneal carcinoma (NPC), and a variety of proliferative disorders that are often seen in the context of immune suppression. This chapter will focus on our efforts to characterize the role of EBV and the virus encoded latent membrane protein 2A (LMP2A) in BL. The molecular characteristics and epidemiology of BL tumors make identification of the viral functions that are important in this particular malignancy difficult, but our recent studies have suggested a key role of LMP2A in the development of BL.