Differential Proteomic Analysis of Endemic and Sporadic Epstein-Barr Virus-Positive and Negative Burkitt Lymphoma

Authors

Nader Kim El-Mallawany, Department of Pediatrics, New York Medical College, Valhalla, NY, United States.
Nancy Day, Department of Pediatrics, Columbia University, New York, NY, United States.
Janet Ayello, Department of Pediatrics, New York Medical College, Valhalla, NY, United States.
Carmella Van de Ven, Department of Pediatrics, New York Medical College, Valhalla, NY, United States.
Kevin Conlon, Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
Damian Fermin, Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
Venkatesha Basrur, Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
Kojo Elenitoba-Johnson, Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
Megan Lim, Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
Mitchell S. Cairo, Department of Pediatrics, New York Medical College, Valhalla, NY, United States; Department of Medicine, New York Medical College, Valhalla, NY, United States; Department of Pathology, New York Medical College, Valhalla, NY, United States; Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, United States; Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, United States. Electronic address: Mitchell_Cairo@nymc.edu.

Author Type(s)

Faculty

DOI

10.1016/j.ejca.2014.10.017

Journal Title

European Journal of Cancer

First Page

92

Last Page

100

Document Type

Article

Publication Date

1-1-2015

Abstract

BACKGROUND: Burkitt lymphoma (BL) is the most common non-Hodgkin lymphoma in children worldwide and the most common paediatric malignancy in sub-Saharan Africa. The endemic (eBL) and sporadic (sBL) variants have distinct epidemiologic and virologic characteristics. Although gene expression studies have defined the transcriptional profiles of both, their proteomic signatures have not been studied. METHODS: We compared the proteomic expression profiles using differential mass spectrometry-based isotope tag for relative and absolute quantitation (iTRAQ) analysis of a cell line representing Epstein-Barr virus (EBV)+ eBL, EBV+ and EBV- sBL, and EBV+/- normal B cells from healthy donors. RESULTS: In total, there were 144 differentially expressed proteins with a statistically significant false discovery rate (FDR) of ⩽0.2. Results revealed over-expression of specific proteins with well-established links to lymphomagenesis such as TUBB2C (FDR 0.05), UCHL1 (FDR 0.05) and HSP90AB1 (FDR 0.1). Distinct characteristics based upon the epidemiologic and virologic subtypes of BL were also identified. In sBL, PCNA (FDR 0.05) and SLC3A2 (FDR 0.1) were significantly over-expressed. In eBL, C1QBP (FDR 0.1) and ENO1 (FDR 0.25) were significantly over-expressed. Comparison of EBV+ to EBV- BL cell lines and B cells revealed significant over-expression of DDX3X (FDR 0.1). Proteins were validated using Western blot analysis. CONCLUSION: Our results suggest unique signal transduction pathways associated with EBV infection and epidemiological subtype of BL that may contribute to lymphomagenesis. These proteomic findings provide potential diagnostic, prognostic and therapeutic links to BL.

Recommended Citation

El-Mallawany, N. K., Day, N., Ayello, J., Van de Ven, C., Conlon, K., Fermin, D., Basrur, V., Elenitoba-Johnson, K., Lim, M., & Cairo, M. S. (2015). Differential Proteomic Analysis of Endemic and Sporadic Epstein-Barr Virus-Positive and Negative Burkitt Lymphoma. European Journal of Cancer, 51 (1), 92-100. https://doi.org/10.1016/j.ejca.2014.10.017