title: Differential proteomic analysis of endemic and sporadic Epstein-Barr virus-positive and negative Burkitt lymphoma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, NY, United States.
authors.forename: Nader Kim
authors.initials: NK
authors.lastname: El-Mallawany
authors.affiliation: Department of Pediatrics, Columbia University, New York, NY, United States.
authors.forename: Nancy
authors.initials: N
authors.lastname: Day
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, NY, United States.
authors.forename: Janet
authors.initials: J
authors.lastname: Ayello
authors.affiliation: Department of Pediatrics, New York Medical College, Valhalla, NY, United States.
authors.forename: Carmella
authors.initials: C
authors.lastname: Van de Ven
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Conlon
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Damian
authors.initials: D
authors.lastname: Fermin
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Venkatesha
authors.initials: V
authors.lastname: Basrur
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Kojo
authors.initials: K
authors.lastname: Elenitoba-Johnson
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Lim
authors.affiliation: 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.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D013058:Mass Spectrometry; D040901:Proteomics; D059467:Transcriptome
keywords: Burkitt lymphoma; EBV; Endemic; Proteomics; Sporadic