Characterization of Epstein-Barr virus-encoded small RNA gene variations in virus associated lymphomas in Northern China

Epstein-Barr virus (EBV)-encoded small RNAs (EBER1 and EBER2) are highly expressed in all forms of EBV latency in EBV-associated malignancies. EBER gene variations and their association with EBV-associated disease still remain poorly characterized. To investigate the patterns of EBER gene variations and their roles in tumorigenesis, EBER gene sequences were analyzed by nested-PCR and DNA sequencing in 101 lymphomas from Northern China, a non-nasopharyngeal carcinoma (NPC) endemic area. In addition, EBV type 1 and type 2 classifications were made by using nested-PCR assays across type-specific regions in the EBNA2 gene. EB-6m was the dominant subtype (95.0%, 96/101) in lymphoma. The distribution of the EBER subtypes in the four lymphoma groups was not significantly different (p > 0.05), neither was that of the EBNA2 type (p > 0.05). Compared with previous data in the same area, the distribution of EBER subtypes in lymphoma was similar to that in EBV-associated gastric carcinoma (EBVaGC) and throat washing (TW) from healthy donors (p > 0.05), but was significantly different from that of NPC. The EBNA2 type distribution between lymphoma and the other three groups was significantly different (p < 0.05). The proportion of type 1 and type 2 dual infections was higher in lymphoma than that in GC, NPC and TW. The mutation 7123nt A → T was identified in 11 of 101 (10.9%, 11/101) lymphomas, significantly more than that in EBV-associated gastric carcinomas (EBVaGC) (0%, 0/50) and throat washings (TWs) from healthy donors (3.3%, 3/92) (p < 0.05). These findings indicate that EBER subtypes may not be associated with pathogenesis of lymphoma, but that a point mutation at position 7123nt (A → T) provides a new area for further exploration. Furthermore it is necessary to investigate the role of EBNA2-subtype mixed infections in the establishment of lymphoma.