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Cancers (Basel). 2018 Jun 2;10(6). pii: E177. doi: 10.3390/cancers10060177.

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

Author information

1
Center for Biologics Evaluation and Research, Food and Drug Administration, White Oak, MD 20993, USA. hsiao-mei.liao@fda.hhs.gov.
2
Center for Biologics Evaluation and Research, Food and Drug Administration, White Oak, MD 20993, USA. hebing.liu@fda.hhs.gov.
3
Center for Biologics Evaluation and Research, Food and Drug Administration, White Oak, MD 20993, USA. lei.haiyan@nih.gov.
4
Center for Biologics Evaluation and Research, Food and Drug Administration, White Oak, MD 20993, USA. bingjie.li@fda.hhs.gov.
5
Center for Biologics Evaluation and Research, Food and Drug Administration, White Oak, MD 20993, USA. pei-ju.chin@fda.hhs.gov.
6
Center for Biologics Evaluation and Research, Food and Drug Administration, White Oak, MD 20993, USA. shien.tsai@gmail.com.
7
Cancer Genetics, Inc., Rutherford, NJ 07070, USA. kishor.bhatia@cgix.com.
8
Laboratorio Stamboulian, Laboratorio Stamboulian, Buenos Aires 1414, Argentina. mgutierrez@stamboulian.com.ar.
9
Department of Pediatric Oncology, St Marcelina Hospital, Sao Paolo 08270-070, Brazil. epelman@uol.com.br.
10
Infections and Immunoepidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. rjbiggar@gmail.com.
11
Noguchi Memorial Institute, Kor Le Bu University, P.O. Box LG 581 Legon, Accra, Ghana. FNkrumah@noguchi.ug.edu.gh.
12
Department of Child Health, University of Ghana, P.O. Box LG 25 Legon, Accra, Ghana. janet.neequaye@yahoo.com.
13
EMBLEM Study, St. Mary's Hospital, Lacor, P.O. Box 180, Gulu, Uganda. ogwang.martin@lacorhospital.org.
14
Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. sjr@jhmi.edu.
15
Center for Biologics Evaluation and Research, Food and Drug Administration, White Oak, MD 20993, USA. shyhching.lo@fda.hhs.gov.
16
Infections and Immunoepidemiology Branch, National Cancer Institute, Bethesda, MD 20892, USA. mbulaits@mail.nih.gov.

Abstract

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.

KEYWORDS:

Africa; Burkitt lymphoma; Epstein-Barr virus; LMP-1; Latin America; next-generation sequencing

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