Atypical Epstein-Barr viral genomic structure in lymphoma tissue and lymphoid cell lines

Weihua Tang, Hongxin Fan, Jane Schroeder, Cherie H. Dunphy, Ronald J. Bryant, Yuri Fedoriw, Margaret L. Gulley

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Epstein-Barr virus (EBV) DNA is found within the malignant cells of some subtypes of lymphoma, and viral presence is being exploited for improved diagnosis, monitoring, and management of affected patients. Recent work suggests that viral genomic polymorphism, such as partial deletion of the viral genome, could interfere with virus detection in tumor tissues. To test for atypical forms of the EBV genome, 98 lymphomas and 6 infected cell lines were studied using a battery of 6 quantitative polymerase chain reaction assays targeting disparate sections of EBV DNA. Fifty of the lymphomas (51%) had no amplifiable EBV DNA, and 38 lymphomas (39%) had low-level EBV infection that was deemed incidental based on EBV-encoded RNA (EBER) in situ hybridization results. The remaining 10 lymphomas (10%) had high EBV loads and EBER localization to malignant cells by EBER in situ hybridization. All 10 represented lymphoma subtypes were previously associated with EBV (Burkitt, diffuse large B-cell, or T-cell type), whereas no remnants of EBV were detected in other lymphoma subtypes (follicular, small lymphocytic, mantle cell, or marginal zone type). Interestingly, 4 of the 10 infected lymphomas had evidence of atypical viral genomes, including 3 of 4 infected T-cell lymphomas with aberrant loss of LMP2 amplicons, and a single diffuse large B-cell lymphoma lacking the central part of the viral genome spanning BamH1W, BZLF1, and EBNA1 gene segments. A reasonable screening strategy for infected malignancy involves applying EBER1 and LMP1 quantitative polymerase chain reaction assays and confirming that values exceeding 2000 copies of EBV per 100,000 cells have EBER localization to malignant cells.

Original languageEnglish (US)
Pages (from-to)91-101
Number of pages11
JournalDiagnostic Molecular Pathology
Volume22
Issue number2
DOIs
StatePublished - Jun 1 2013

Keywords

  • Cell line
  • DNA polymorphism
  • Epstein-Barr virus
  • Non-Hodgkin lymphoma
  • Screening test
  • Viral load assay

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Tang, W., Fan, H., Schroeder, J., Dunphy, C. H., Bryant, R. J., Fedoriw, Y., & Gulley, M. L. (2013). Atypical Epstein-Barr viral genomic structure in lymphoma tissue and lymphoid cell lines. Diagnostic Molecular Pathology, 22(2), 91-101. https://doi.org/10.1097/PDM.0b013e318273fb43