Department of Pediatrics; Department of Quantitative Health Sciences
Hemic and Lymphatic Diseases | Immune System Diseases | Immunology and Infectious Disease | Neoplasms | Pediatrics | Virus Diseases
BACKGROUND: Epstein Barr virus (EBV) is a gammaherpesvirus that is associated with nasopharyngeal carcinoma (NPC) and endemic Burkitt lymphoma (eBL). EBV carries several latent genes that contribute to oncogenesis including the latent membrane protein 1 (LMP-1), a known oncogene and constitutively active CD40 homolog. Variation in the C terminal region of LMP-1 has been linked to NPC pathogenesis, but little is known regarding LMP-1 variation and eBL.
RESULTS: In the present study, peripheral blood samples were obtained from 38 eBL patients and 22 healthy controls in western Kenya, where the disease is endemic. The LMP-1 C-terminal region from these samples was sequenced and analyzed. The frequency of a 30 base pair deletion of LMP-1 previously linked to NPC was not associated with eBL compared to healthy controls. However a novel LMP-1 variant was identified, called K for Kenya and for the G318K mutation that characterizes it. The K variant LMP-1 was found in 40.5% of eBL sequences and 25.0% of healthy controls. All K variant sequences contained mutations in both of the previously described minimal T cell epitopes in the C terminal end of LMP-1. These mutations occurred in the anchor residue at the C-terminal binding groove of both epitopes, a pocket necessary for MHC loading.
CONCLUSIONS: Overall, our results suggest that there is a novel K variant of LMP-1 in Kenya that may be associated with eBL. Further studies are necessary to determine the functional implications of the LMP-1 variant on early events in eBL genesis.
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Copyright 2013 Wohlford et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
Wohlford EM, Asito AS, Chelimo K, Sumba PO, Baresel PC, Oot RA, Moormann AM, Rochford R. Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya. Infect Agent Cancer. 2013 Sep 9;8(1):34. doi: 10.1186/1750-9378-8-34. Link to article on publisher's site
Infectious agents and cancer
Wohlford, Eric M.; Asito, Amolo S.; Chelimo, Kiprotich; Sumba, Peter Odada; Baresel, Paul C.; Oot, Rebecca A.; Moormann, Ann M.; and Rochford, Rosemary A., "Identification of a novel variant of LMP-1 of EBV in patients with endemic Burkitt lymphoma in western Kenya" (2013). University of Massachusetts Medical School Faculty Publications. 296.