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Epstein-Barr virus (EBV) genotyping in EBV-associated lesions

Epstein-Barr virus (EBV) genotyping in EBV-associated lesions

Tong, Hung-Man; To, Ka-Fai. The Chinese University of Hong Kong (Hong Kong), 2004. 2004. 3162582.

Abstract (summary)

A comprehensive genotyping of Epstein-Barr virus (EBV) was performed in various EBV-associated lesions including infectious mononucleosis (IM), natural killer/T-cell (NK/T) cell lymphoma, nasopharyngeal carcinoma (NPC), post-transplant lymphoproliferative disorders (PTLD), reactive hemophagocytic syndrome (RHS), and EBV-positive healthy donors. EBV typing according to the EBNA 3C region demonstrated that EBV-1 is prevalent in Hong Kong, irrespective of the disease groups. It was detected in 87.8% of EBNA3c positive mouth gargle samples from healthy donors, and more than 95% of the specimens from IM, NK/T cell lymphoma, NPC, PTLD and RHS.

Genotyping of the EBV LMP1 gene revealed that the 30-bp deletion variant (DV) was predominant in Hong Kong. It was statistically associated with NK/T cell lymphoma. Moreover, the DV-335Asp strain appeared more frequently in NK/T cell lymphoma than in healthy donors (p = 0.01). This specific EBV strain may be important in carcinogenesis.

The amino terminal domain of LMP2A was generally conserved with a few base pair changes in an occasional isolates. There was no significant association of a particular LMP2A variant with any of the disease groups. The pattern of LMP2A polymorphism did not segregate with EBV type 1 or type 2.

Two major subtypes of the promoter sequence of BZLF1 Zp-P and Zp-V3 were identified. Although Zp-V3 is detectable in nonmalignant samples, its association with NPC is statistically significant. Functional study showed that the Zp-V3 had a lower activity in response to lytic stimuli in NPC and normal NP cell line. EBV with Zp-V3 variant might associate with a tight latency which was less responsive to lytic stimulants. On the other hand, Zp-P and V4 variants might exert an anti-neoplastic effect by promoting lytic replication. Given the premises of strong association of NPC with Epstein-Barr virus (EBV), detection of EBV has been developed as a molecular marker for NPC. We developed a non-invasive approach to collect exfoliative cytologic specimens from nasopharyngeal region using a specially designed brush. EBV DNA quantity in NP brushing samples from NPC patients (median 8.94 copies/actin) was significantly higher than that of controls (median 0 copies/actin) (p < 0.0001). Elevated EBV DNA level in brushing samples as a tumor marker had a sensitivity of 96.4% and specificity of 96.2% for NPC detection. In brushing samples of NPC patients, the frequencies of DAP-kinase, RASSF1A and p16 promoter hypermethylation were 50.0%, 39.3% and 46.4% respectively. Seventy-eight percent of cases showed methylation of at least one gene. No aberrant hypermethylation was detected in control samples. Our study demonstrated the feasibility of detecting multiple molecular tumor markers in NP brushing samples and a high sensitivity and specificity for NPC detection.

keyword Health and environmental sciences, Epstein-Barr virus, Genotyping, Lesions, BZLF1