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

Wen Yi Wang, Yi Chih Chien, Jian Sheng Jan, Chun Mei Chueh, Jin Ching Lin

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Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)2586-2590
Number of pages5
JournalClinical Cancer Research
Volume8
Issue number8
Publication statusPublished - 2002 Jan 1

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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