title: Atypical Epstein-Barr viral genomic structure in lymphoma tissue and lymphoid cell lines.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Weihua
authors.initials: W
authors.lastname: Tang
authors.forename: Hongxin
authors.initials: H
authors.lastname: Fan
authors.forename: Jane
authors.initials: J
authors.lastname: Schroeder
authors.forename: Cherie H
authors.initials: CH
authors.lastname: Dunphy
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bryant
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fedoriw
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gulley
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D008214:Lymphocytes / Q000821:virology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000821:virology*; D016399:Lymphoma, T-Cell / Q000175:diagnosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral; D014763:Viral Matrix Proteins