Abstract
Latent membrane protein 2A (LMP2A), expressed in most Epstein-Barr virus (EBV)-associated malignancies, has been demonstrated to be responsible for the maintenance of latent infection and epithelial cell transformation. Besides, it could also act as the target for a CTL-based therapy for EBV-associated malignancies. In the present study, sequence variations of LMP2A in EBV-associated gastric carcinoma (EBVaGC) and healthy EBV carriers from Guangzhou, southern China, where nasopharyngeal carcinoma (NPC) is endemic, were investigated. Widespread sequence variations in the LMP2A gene were found, with no sequence identical to the B95.8 prototype. No consistent mutation was detected in all isolates. The immunoreceptor tyrosine-based activation motif (ITAM) and PY motifs in the amino terminus of LMP2A were strictly conserved, suggesting their important roles in virus infection; while 8 of the 17 identified CTL epitopes in the transmembrane region of LMP2A were affected by at least one point mutation, which may implicate that the effect of LMP2A polymorphisms should be considered when LMP2A-targeted immunotherapy is conducted. The polymorphisms of LMP2A in EBVaGC in gastric remnant carcinoma (GRC) were for the first time investigated in the world. The LMP2A sequence variations in EBVaGC in GRC were somewhat different from those in EBVaGC in conventional gastric carcinoma. The sequence variations of LMP2A in EBVaGC were similar to those in throat washing of healthy EBV carriers, indicating that these variations are due to geographic-associated polymorphisms rather than EBVaGC-associated mutations. This, to our best knowledge, is the first detailed investigation of LMP2A polymorphisms in EBVaGC in Guangzhou, southern China, where NPC is endemic.
Highlights
Epstein-Barr virus (EBV) is a ubiquitous herpes virus that was originally identified in a human Burkitt lymphoma cell line [1]
We found that the proportion of EBV-associated gastric carcinoma (EBVaGC) in gastric remnant carcinoma (GRC) was significantly higher than that in conventional gastric carcinoma (CGC) which occurs in the intact stomach in Guangzhou (30.8% vs. 6.7%)
The present study described the expression of Latent membrane protein 2A (LMP2A) in EBVaGC and for the first time revealed the polymorphisms of LMP2A in EBVaGC in Guangzhou, southern China, which is an endemic area of nasopharyngeal carcinoma (NPC)
Summary
Epstein-Barr virus (EBV) is a ubiquitous herpes virus that was originally identified in a human Burkitt lymphoma cell line [1]. It is implicated in the etiology of human lymphoid neoplasms including Burkitt lymphoma, Hodgkin lymphoma, and B-cell lymphomas among immunosuppressed patients [2]. EBV has been suspected to cause epithelial malignancies such as nasopharyngeal carcinoma (NPC) and a subset of gastric carcinoma which is defined as EBV-associated gastric carcinoma (EBVaGC) [2]. The first large study (.500 cases) was conducted in Japan, in which EBVaGC accounted for 6.9% of the cases (67 of 970 cases) [6]. Besides Japan, van Beek et al [7]
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