Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Epstein Barr virus-positive (EBV+) B cell lymphomas can arise in immunosuppressed individuals, such as organ transplant recipients in the context of post-transplant lymphoproliferative disorder (PTLD). There are currently limited treatment options for EBV+ B lymphomas in PTLD, efficacies are highly variable, and treatment-related mortality is a serious concern. The prevailing paradigm is that EBV DNA exclusively persists in a closed circular (episomal) form, while expressing a specific set of “latency program” viral proteins that contribute to tumorigenesis, in latently-infected B lymphoma cells.
Here we investigated the status of the EBV genome in EBV+ B lymphoma cell lines derived from patients with PTLD.
*Methods: We assessed the EBV genomic DNA status in B cell lymphomas through EBV-specific fluorescence in situ hybridization (FisH) and comprehensive mitotic cell analyses of EBV FisH signal types followed by chromosome mapping of EBV integrated-specific signals. EBV genomic DNA status was also evaluated by EBV-specific DNA (Southern) blotting of BamHI, EcoRI and BgIll-digested genomic DNA fragments with an EBV DNA probe unique to the left-of-TR viral region.
*Results: We determined that the EBV genomic DNA is physically integrated into host human genomic DNA at recurring sites in three of three EBV+ transplant B lymphoma cell lines, along with low levels of extrachromosomal, episomal EBV. SAM analysis of virus-specific cytogenetic data for >100 nuclei indicated statistically-significant (p<0.05) recurrent EBV integration signals at human chromosomes sites 4p/q, 6q, 13q, and 16p/q. Viral DNA Southern blots verified the intrachromosomal, linear EBV DNA state in the patient-derived EBV+ B lymphoma cells. We are currently applying deep whole-genome sequencing of EBV+ B lymphoma DNA and BatVI to determine the precise host genetic sites that are disrupted by EBV DNA in B lymphoma cells.
*Conclusions: EBV is detected in a host DNA-integrated state in latently-infected B lymphoma cells from patients with PTLD. Furthermore, these viral integrations occur at recurrent human host lymphoma genomic sites. A comprehensive exploration of the viral integration-based mechanism of host B cell dysregulation and lymphoma development may help to define new targets in the treatment of EBV+ B cell lymphomas in solid organ recipients with PTLD.
To cite this abstract in AMA style:McPherson MC, Martinez OM. Epstein Barr Virus DNA Integration in B Cell Lymphomas of Post-Transplant Lymphoproliferative Disorder [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/epstein-barr-virus-dna-integration-in-b-cell-lymphomas-of-post-transplant-lymphoproliferative-disorder/. Accessed April 15, 2021.
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