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

serial: '5'
sid: '150772'
uuid: a3c7d132-125a-4b6c-95a6-80d03a9430f9
uri: /nci/ealv/venue/abstract
created: '1756920501'
completed: '1756920501'
changed: '1756920501'
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langcode: en
webform_id: ebv_ass_lym_consorti_abstrac
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entity_id: '1883'
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notes: ''
metatag: meta
data:
  degree_s_: PhD
  email: ahaluckk@stanford.edu
  first_name: Ashley
  keywords_abstracts: 'EBV, LMP1, PTLD'
  last_name: Haluck-Kangas
  middle_initial: ''
  organization: 'Stanford University School of Medicine'
  organization_address:
    address: ''
    address_2: ''
    city: 'Stanford, CA'
    country: ''
    postal_code: ''
    state_province: ''
  summary: '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.'
  title: 'Post-Doctoral Fellow'
  ttile: 'Characterization of Latent Membrane Protein 1 Diversity in EBV+ Post Transplant Lymphoproliferative Disease'