EBV Conference 2008 Guangzhou - Baylor College of Medicine

104 (RegID: 1292)
Jaap Middeldorp
Institution: VU University medical center, Dept.Pathology
e-mail: j.middeldorp@vumc.nl
CONSERVED MUTATION OF EPSTEIN-BARR VIRUS-ENCODED BARF1 GENE IN
INDONESIAN NASOPHARYNGEAL CARCINOMA CASES.
Susanna H. Hutajulu, Servi JC Stevens, Sandra AWM Verkuijlen, Astrid E. Greijer, Sofia M. Haryana ,
Jaap M Middeldorp.
Posterabstract:
Background: BamHI-A rightward frame-1 (BARF1) is a potent carcinoma-specific EBV oncogene, but
little is known about its genetic diversity in nasopharyngeal carcinoma (NPC).
Objective: This study aimed at defining the sequence of BARF1 in NPC compared to other EBV-related
diseases. The correlation of BARF1 sequence diversity with viral load, EBV genotyping, and presence of
antibodies to EBV was determined.
Method: Nasopharyngeal brushings and tissues from 56 NPC cases or blood from 15 patients with other
EBV-driven disorders, and 7 spontaneous EBV positive B-cell lines (LCL) from healthy indonesian
individuals were included. Purified DNA was analysed by PCR-direct sequencing. EBV-DNA viral load
and EBV strain typing (based on EBNA2 sequence) were analyzed by PCR. Serology using
IgA-[EBNA1/VCAp18] ELISA and IgG immunoblot analysis was done on all NPC sera.
Results: Most NPC isolates showed specific BARF1 nucleotide changes compared to prototype B95-8. At
the protein level the mutations led to 3 main substitutions: V29A, W72G, H130R. Amino acid conversions
were shown by 80.3% of NPC samples compared to 33.3% of non-NPC samples (p= 0.001). Amino acid
changes did not associate with IgA ELISA titer (p= 0.495) and immunoblot diversity (p= 0.187). Almost
all NPC and non-NPC samples contained EBV type 1. One NPC sample was mixed-type and 1 non-NPC
sample was type 2. The viral load of either NPC or non-NPC samples was high, but not related to a
particular BARF1 variant.
Conclusion: The EBV BARF1 gene shows genetic diversity which is more frequently present in NPC than
in non-NPC EBV-related samples. These sequence variants may exist in the regional population as a
predisposition of NPC. The functional implications for BARF1 mutations remain to be defined.
EBV Conference 2008 Guangzhou
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