High frequency of Epstein Barr virus latent membrane protein-1 30 bp deletion in a series of pediatric malignancies in Argentina

Arch Virol. 2004 Aug;149(8):1515-26. doi: 10.1007/s00705-004-0311-1. Epub 2004 Apr 15.

Abstract

Epstein Barr virus widely infects human populations and remains mostly asymptomatic; however, it has been associated with several malignancies. The EBV-encoded latent membrane protein-1 has been involved in neoplasic transformation; a 30-bp deletion and several mutations in the COOH-terminal domain have been associated with histopathological and clinical disease features.

Objective: To analyze and correlate the presence of mutations and a 30-bp deletion with the influence of LMP-1 on tumorigenicity in a population of EBV+ pediatric malignancies.

Methods: We studied EBV presence by LMP-1 immunohistochemistry, EBERs in situ hybridization and PCR in fresh and formalin-fixed paraffin-embedded tissue samples from 10 Hodgkin's lymphomas, 6 non-Hodgkin's lymphomas, 4 undifferentiated nasopharyngeal carcinomas. Eighteen out of 20 samples were sequenced. Eight fresh normal lymphoid tissue samples and 3 peripheral blood samples were analyzed.

Results: All cases were EBV positive. EBV typing rendered 12 EBV-1 and 8 EBV-2. Del-LMP-1 was detected in 15/20 EBV related malignancies, as well as in 4/11 control tissues. A high percentage of patients showed point mutations previously described. The presence of del-LMP-1 and point mutations failed to correlate with clinical course.

Conclusions: We found a marked incidence of del-LMP-1 (75%) in our series. However, we failed to find any correlation between histological aggressiveness of malignancies and the presence of del-LMP-1 and point mutations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Argentina
  • Base Sequence
  • Carcinoma / pathology
  • Carcinoma / virology*
  • Child
  • DNA, Viral / genetics*
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / pathogenicity
  • Hodgkin Disease / pathology
  • Hodgkin Disease / virology*
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology
  • Lymph Nodes / virology*
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / virology*
  • Male
  • Molecular Sequence Data
  • Mutation
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology*
  • Oncogene Proteins, Viral / analysis
  • Oncogene Proteins, Viral / genetics*
  • Polymerase Chain Reaction
  • Sequence Alignment
  • Viral Matrix Proteins / analysis
  • Viral Matrix Proteins / genetics*
  • Virus Latency

Substances

  • DNA, Viral
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Oncogene Proteins, Viral
  • Viral Matrix Proteins