title: Epidemiology: clues to the pathogenesis of Burkitt lymphoma.
abstract: The two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria--BL incidence relates to the malaria transmission rate--and early infection by Epstein-Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component of lymphomagenesis in BL. The critical event in lymphomagenesis is the creation of a MYC translocation, bringing the MYC gene into juxtaposition with immunoglobulin genes and causing its ectopic expression, thereby driving the proliferation of BL cells. It is highly likely that such translocations are mediated by the activation-induced cytidine deaminase (AID) gene, which is responsible for hypervariable region mutations as well as class switching. Stimulation of the Toll-like receptor 9 by malaria-associated agonists induces AID, providing a mechanism whereby malaria could directly influence BL pathogenesis. EBV-containing cells must reach the memory cell compartment in order to survive throughout the life of the individual, which probably requires traversal of the germinal centre. Normally, cells that do not produce high affinity antibodies do not survive this passage, and are induced to undergo apoptosis. EBV, however, prevents this, and in doing so may also enhance the likelihood of survival of rare translocation-containing cells.
authors.affiliation: International Network for Cancer Treatment and Research, Rue Engeland 642, Brussels, Belgium. imagrath@inctr.be
authors.forename: Ian
authors.initials: I
authors.lastname: Magrath
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002051:Burkitt Lymphoma / Q000150:complications / Q000453:epidemiology* / Q000209:etiology*; D004777:Environment; D020031:Epstein-Barr Virus Infections / Q000150:complications; D006801:Humans; D008288:Malaria / Q000150:complications; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: D016271:Proto-Oncogene Proteins c-myc