EBV-Associated Lymphoma Consortium Annual Meeting (Abstract): Submission #5

Submission information
Submission Number: 5
Submission ID: 150772
Submission UUID: a3c7d132-125a-4b6c-95a6-80d03a9430f9
Submission URI: /nci/ealv/venue/abstract

Created: Wed, 09/03/2025 - 13:28
Completed: Wed, 09/03/2025 - 13:28
Changed: Wed, 09/03/2025 - 13:28

Remote IP address: 10.208.24.230
Submitted by: Anonymous
Language: English

Is draft: No
Presenter Information
Ashley
{Empty}
Haluck-Kangas
PhD
Post-Doctoral Fellow
Stanford University School of Medicine
Stanford, CA
Abstract Information
EBV, LMP1, PTLD
Characterization of Latent Membrane Protein 1 Diversity in EBV+ Post Transplant Lymphoproliferative Disease
EBV is associated with the development of Post-Transplant Lymphoproliferative Disease (PTLD) in immunosuppressed solid organ and hematopoietic stem cell recipients. Prior studies from our group identified mutations (G212S and S366T) in latent member protein 1 (LMP1) of EBV that were associated with EBV+ PTLD (OR=11.7). However, some matched controls also carried both LMP1 mutations and did not develop EBV+ PTLD. Therefore, we analyzed LMP1 in EBV+ PTLD cases with the G212S and S366T mutations (n=28), EBV-seropositive transplant controls without PTLD that also have the two LMP1 mutations (n=48), and EBV-seropositive transplant controls without the LMP1 mutations (n=11) to determine if other non-synonymous changes were associated with EBV+ PTLD. We identified three highly mutated sites in EBV+ PTLD LMP1 (S309N, Q334R, and L338S or L338P), however these amino acid changes were also seen at similar frequencies in LMP1 from controls. Patients with EBV+ PTLD had fewer non-synonymous changes (mean 7.57, SE 0.551) in LMP1 compared to controls (mean 9.08, SE 0.506), and there were no novel non-synonymous changes in LMP1 associated with EBV+ PTLD. We also compared the frequency of the well-described 10 amino acid deletion in LMP1 and while the deletion was more common in LMP1 from EBV+ PTLD cases, there was no significant difference in the deletion frequency in cases and controls. Finally, we analyzed the HLA-E*01:03 epitope (GGDPHLPTL) previously characterized by our group to strongly bind and stabilize HLA-E. We did not observe any significant enrichment of nonsynonymous mutations in the LMP1 sequence encoding this motif in cases or controls. Our data demonstrates that considerable genetic variability exists in the c-terminal domain of LMP1. However, no specific variation appears to predict the development of EBV+ PTLD. It is possible that predictive and/or functional genetic variants may occur in other EBV genes which is the focus of on-going studies.
{Empty}