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.