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Consistent sequence variation of Epstein-Barr virus nuclear antigen 1 in primary tumor and peripheral blood cells of patients with nasopharyngeal carcinoma.

AbstractPURPOSE:
Nasopharyngeal carcinoma (NPC) has been proven as a cancer associated with Epstein-Barr virus (EBV). This study was performed to examine sequence variations of the EBV nuclear antigen 1 gene (EBNA-1) in primary tumor and peripheral-blood cells of NPC patients from Taiwan.
EXPERIMENTAL DESIGN:
DNA extracted from freshly frozen tumor tissues and corresponding peripheral-blood cells of 13 previously untreated NPC patients were subjected to PCR and direct sequencing using EBNA-1-specific primers. We compared the sequence data and analyzed the clinical outcomes.
RESULTS:
We obtained a 100% positive-detection rate of EBV DNA in the primary tumors of all patients irrespective of the degree of differentiation. The EBNA-1 gene of all tumor samples was the "V-val" strain, showing the same clustered point mutations. They included 21 nucleotide exchanges, leading to 14 amino-acid mutations and 6 silent exchanges, relative to B95-8 cell line. Two of 13 tumors exhibited an additional point mutation at codon 585. EBV DNA was also detected in peripheral-blood cells of 9 of 13 patients under our experimental conditions. Direct-sequencing data showed match alterations of EBNA-1 gene between the primary tumor and peripheral-blood cells. Tumor relapse was observed in four of nine patients with detectable EBNA-1 DNA in their peripheral-blood cells, whereas none of the four patients without detectable EBNA-1 DNA in their peripheral-blood cells developed tumor relapse.
CONCLUSIONS:
Results of the current study represents the first demonstration of consistent sequence variation of EBNA-1 in primary tumors and peripheral-blood cells. Clinical observations support that the presence of EBV DNA in the peripheral-blood cells may arise from disseminated cancer cells, resulting in a higher relapse rate and poor prognosis.
AuthorsWen-Yi Wang, Yi-Chih Chien, Jian-Sheng Jan, Chun-Mei Chueh, Jin-Ching Lin
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 8 Issue 8 Pg. 2586-90 (Aug 2002) ISSN: 1078-0432 [Print] United States
PMID12171888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA, Viral
  • Epstein-Barr Virus Nuclear Antigens
  • EBV-encoded nuclear antigen 1
Topics
  • Carcinoma (mortality, virology)
  • DNA, Viral
  • Epstein-Barr Virus Nuclear Antigens (genetics)
  • Humans
  • Lymphocytes (virology)
  • Models, Genetic
  • Nasopharyngeal Neoplasms (mortality, virology)
  • Point Mutation
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Species Specificity
  • Treatment Outcome

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