title: Epstein-Barr virus promotes genomic instability in Burkitt's lymphoma.
abstract: Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human malignancies but the mechanisms of oncogenesis remain largely unknown. Genomic instability and chromosomal aberrations are hallmarks of malignant transformation. We report that EBV carriage promotes genomic instability in Burkitt's lymphoma (BL). Cytogenetic analysis of EBV- and EBV+ BL lines and their sublines derived by EBV conversion or spontaneous loss of the viral genome revealed a significant increase in dicentric chromosomes, chromosome fragments and chromatid gaps in EBV-carrying cells. Expression of EBV latency I was sufficient for this effect, whereas a stronger effect was observed in cells expressing latency III. Telomere analysis by fluorescent in situ hybridization revealed an overall increase of telomere size and prevalence of telomere fusion and double strand-break fusion in dicentric chromosomes from EBV+ cells. Phosphorylated H2AX, a reporter of DNA damage and ongoing repair, was increased in virus-carrying cells in the absence of exogenous stimuli, whereas efficient activation of DNA repair was observed in both EBV+ and EBV- cells following treatment with etoposide. These findings point to induction of telomere dysfunction and DNA damage as important mechanisms for EBV oncogenesis.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S A
authors.initials: SA
authors.lastname: Kamranvar
authors.forename: B
authors.initials: B
authors.lastname: Gruhne
authors.forename: A
authors.initials: A
authors.lastname: Szeles
authors.forename: M G
authors.initials: MG
authors.lastname: Masucci
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics* / Q000821:virology*; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000648:ultrastructure; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D042822:Genomic Instability; D004854:Herpesvirus 4, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D010766:Phosphorylation; D016615:Telomere / Q000648:ultrastructure*; D017735:Virus Latency
chemical_list: C468783:H2AX protein, human; D006657:Histones