Abstract: OBJECTIVE: To characterize the sequence variations of Epstein-Barr virus(EBV)-encoded latent membrane protein 1(LMP1) gene in extranodal NK/T cell lymphoma,nasal type (ENKTL) and healthy donors in Shandong province and to explore the association of LMP1 variants with ENKTL. METHODS: Nested-PCR and DNA sequencing were used to analyze the gene sequences of LMP1 in isolates from 47 ENKTL tissues and 70 throat washing samples of healthy controls in Shandong province. The sequences of LMP1 were compared with the prototype B95-8 strain and classified according to the signature changes and the phylogenetic tree. The distribution of LMP1 variants was compared between ENKTL and healthy controls. RESULTS: A total of 117 isolates from 47 ENKTL and 70 healthy controls were successfully sequenced and three main subtypes of LMP1 gene,China 1,China 2 and Med-,were identified. The frequencies of China 1,China 2 and Med- in ENKTL were 85.1%,8.5% and 4.3%,respectively,and those in healthy controls were 65.7%,5.7% and 21.4%,respectively. Another one(2.1%) ENKTL isolate and 5(7.2%) healthy controls isolates were recombinant strains of different subtypes. The distribution of LMP1 subtypes between ENKTL and healthy controls was significantly different (P=0.003). The frequencies of XhoI(-) (loss of an XhoI site in N-terminus of LMP1) and del-LMP1 (30 bp deletion in C-terminus of LMP1) in ENKTL were 95.7% and 85.1%,respectively,which were significantly higher than those in healthy controls (74.3% and 67.1%,P=0.003 and 0.029,respectively). CONCLUSION: China 1,Xho I(-) and del-LMP1 were the major LMP1 subtypes in ENKTL and may associate with the susceptibility of ENKTL.

Key words: Epstein-Barr virus, lymphoma, extranodal NK/T cell, latent membrane protein 1, gene polymorphism