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Molecular epidemiology of EBNA-1 substrains of Epstein-Barr virus in posttransplant lymphoproliferative disorders which have infrequent p53 mutations.

Abstract
Posttransplant lymphoproliferative disorders (PTLDs), which are highly associated with Epstein-Barr virus infection, have a low frequency of molecular genetic abnormalities. Recently it has been suggested certain EBV substrains may be associated with specific lymphoma subtypes. The goals of our study were two fold: 1) to determine the prevalence of EBNA-1 substrains and prognostic utility in PTLD and 2) to determine the incidence of p53 gene mutations and p53 protein overexpression in 32 EBV-positive PTLD cases. Tumor DNA was sequenced to identify EBNA-1 substrains at codon 487 and p53 gene mutations in exons 5-8. The PTLD samples contained the following EBNA-1 substrains: P-thr in 17/32 (53%), P-ala in 11/32 (34%), and V-leu in 4/32 (13%). More heterogeneity within major subtypes was seen in the PTLD cases than in the referral group. A second group of 25 referral (non-PTLD) samples including infectious mononucleosis (6) and sequential EBV positive virology samples (19) contained P-thr in 17/25 (68%); P-ala in 2/25 (8%); and V-leu in 6/25 (24%). In the 29 B-cell PTLD the time to presentation was an average of 13.3 months in the P-ala group, 16.6 months in the P-thr group, and 40.6 months in the V-leu group: (p>0.05). There was no difference in survival in patients (median overall--60 months) between the three different substrains of EBNA-1 (Log rank test, p=0.39). One of 31 (4.1%) cases (a diffuse large cell B-cell) had a p53 mutation. Seven of 31 (23%) cases (all B-cell), including the p53 mutated case, had over-expression of p53 protein. We conclude EBNA-1 substrains vary in PTLD and suggest the pattern reflects the geographical incidence of substrains in the region. We also conclude p53 mutations are not a significant molecular genetic abnormality in PTLD.
AuthorsT C Greiner, A A Abou-Elella, B N Smir, A Orazi, S Hinrichs, J Anderson, T Gross, P Bierman, R Hauke
JournalLeukemia & lymphoma (Leuk Lymphoma) Vol. 38 Issue 5-6 Pg. 563-76 (Aug 2000) ISSN: 1042-8194 [Print] SWITZERLAND
PMID10953978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Topics
  • Epstein-Barr Virus Infections (etiology, genetics, virology)
  • Genes, p53
  • Herpesvirus 4, Human (genetics, isolation & purification)
  • Humans
  • Immunosuppression (adverse effects)
  • Lymphoproliferative Disorders (etiology, genetics, mortality, virology)
  • Mutation
  • Organ Transplantation (adverse effects)

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