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Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda

Epstein-Barr virus (EBV) is linked to several cancers, including endemic Burkitt lymphoma (eBL), but causal variants are unknown. We recently reported novel sequence variants in the LMP-1 gene and promoter in EBV genomes sequenced from 13 of 14 BL biopsies. Alignments of the novel sequence variants...

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Autores principales: Liao, Hsiao-Mei, Liu, Hebing, Lei, Heiyan, Li, Bingjie, Chin, Pei-Ju, Tsai, Shien, Bhatia, Kishor, Gutierrez, Marina, Epelman, Sidnei, Biggar, Robert J., Nkrumah, Francis, Neequaye, Janet, Ogwang, Martin D., Reynolds, Steven J., Lo, Shyh-Ching, Mbulaiteye, Sam M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024959/
https://www.ncbi.nlm.nih.gov/pubmed/29865259
http://dx.doi.org/10.3390/cancers10060177
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author Liao, Hsiao-Mei
Liu, Hebing
Lei, Heiyan
Li, Bingjie
Chin, Pei-Ju
Tsai, Shien
Bhatia, Kishor
Gutierrez, Marina
Epelman, Sidnei
Biggar, Robert J.
Nkrumah, Francis
Neequaye, Janet
Ogwang, Martin D.
Reynolds, Steven J.
Lo, Shyh-Ching
Mbulaiteye, Sam M.
author_facet Liao, Hsiao-Mei
Liu, Hebing
Lei, Heiyan
Li, Bingjie
Chin, Pei-Ju
Tsai, Shien
Bhatia, Kishor
Gutierrez, Marina
Epelman, Sidnei
Biggar, Robert J.
Nkrumah, Francis
Neequaye, Janet
Ogwang, Martin D.
Reynolds, Steven J.
Lo, Shyh-Ching
Mbulaiteye, Sam M.
author_sort Liao, Hsiao-Mei
collection PubMed
description Epstein-Barr virus (EBV) is linked to several cancers, including endemic Burkitt lymphoma (eBL), but causal variants are unknown. We recently reported novel sequence variants in the LMP-1 gene and promoter in EBV genomes sequenced from 13 of 14 BL biopsies. Alignments of the novel sequence variants for 114 published EBV genomes, including 27 from BL cases, revealed four LMP-1 variant patterns, designated A to D. Pattern A variant was found in 48% of BL EBV genomes. Here, we used PCR-Sanger sequencing to evaluate 50 additional BL biopsies from Ghana, Brazil, and Argentina, and peripheral blood samples from 113 eBL cases and 115 controls in Uganda. Pattern A was found in 60.9% of 64 BL biopsies evaluated. Compared to PCR-negative subjects in Uganda, detection of Pattern A in peripheral blood was associated with eBL case status (odds ratio [OR] 31.7, 95% confidence interval: 6.8–149), controlling for relevant confounders. Variant Pattern A and Pattern D were associated with eBL case status, but with lower ORs (9.7 and 13.6, respectively). Our results support the hypothesis that EBV LMP-1 Pattern A may be associated with eBL, but it is not the sole associated variant. Further research is needed to replicate and elucidate our findings.
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spelling pubmed-60249592018-07-09 Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda Liao, Hsiao-Mei Liu, Hebing Lei, Heiyan Li, Bingjie Chin, Pei-Ju Tsai, Shien Bhatia, Kishor Gutierrez, Marina Epelman, Sidnei Biggar, Robert J. Nkrumah, Francis Neequaye, Janet Ogwang, Martin D. Reynolds, Steven J. Lo, Shyh-Ching Mbulaiteye, Sam M. Cancers (Basel) Article Epstein-Barr virus (EBV) is linked to several cancers, including endemic Burkitt lymphoma (eBL), but causal variants are unknown. We recently reported novel sequence variants in the LMP-1 gene and promoter in EBV genomes sequenced from 13 of 14 BL biopsies. Alignments of the novel sequence variants for 114 published EBV genomes, including 27 from BL cases, revealed four LMP-1 variant patterns, designated A to D. Pattern A variant was found in 48% of BL EBV genomes. Here, we used PCR-Sanger sequencing to evaluate 50 additional BL biopsies from Ghana, Brazil, and Argentina, and peripheral blood samples from 113 eBL cases and 115 controls in Uganda. Pattern A was found in 60.9% of 64 BL biopsies evaluated. Compared to PCR-negative subjects in Uganda, detection of Pattern A in peripheral blood was associated with eBL case status (odds ratio [OR] 31.7, 95% confidence interval: 6.8–149), controlling for relevant confounders. Variant Pattern A and Pattern D were associated with eBL case status, but with lower ORs (9.7 and 13.6, respectively). Our results support the hypothesis that EBV LMP-1 Pattern A may be associated with eBL, but it is not the sole associated variant. Further research is needed to replicate and elucidate our findings. MDPI 2018-06-02 /pmc/articles/PMC6024959/ /pubmed/29865259 http://dx.doi.org/10.3390/cancers10060177 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liao, Hsiao-Mei
Liu, Hebing
Lei, Heiyan
Li, Bingjie
Chin, Pei-Ju
Tsai, Shien
Bhatia, Kishor
Gutierrez, Marina
Epelman, Sidnei
Biggar, Robert J.
Nkrumah, Francis
Neequaye, Janet
Ogwang, Martin D.
Reynolds, Steven J.
Lo, Shyh-Ching
Mbulaiteye, Sam M.
Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda
title Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda
title_full Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda
title_fullStr Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda
title_full_unstemmed Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda
title_short Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda
title_sort frequency of ebv lmp-1 promoter and coding variations in burkitt lymphoma samples in africa and south america and peripheral blood in uganda
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024959/
https://www.ncbi.nlm.nih.gov/pubmed/29865259
http://dx.doi.org/10.3390/cancers10060177
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