EB病毒潜伏膜蛋白1基因多态性与NK/T细胞淋巴瘤的相关性  

Association between polymorphisms of latent membrane protein 1 gene of Epstein-Barr virus and NK/T cell lymphoma

作　　者：刘芡芡 孙玲玲[2] 王宏[1,3] 吴越[4] 王如欣[4] 罗兵[1] 王云[1] 

机构地区：[1]青岛大学医学院微生物教研室,山东青岛266021 [2]青岛大学附属医院病理科,山东青岛266003 [3]济南军区青岛第一疗养院检验科,山东青岛266071 [4]青岛大学医学院公共卫生系,山东青岛266021

出　　处：《癌变．畸变．突变》2015年第4期266-271,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金资助项目(81171571);青岛市科技计划项目(13-1-3-50-nsh)

摘　　要：目的:探讨EB病毒(EBV)潜伏膜蛋白1(LMP1)基因变异与山东地区结外鼻型NK/T细胞淋巴瘤(ENKTL)的相关性。方法:采用巢式PCR和DNA测序检测山东地区EBV阳性ENKTL组织(47例)和健康成年人咽漱液(70例)中LMP1全长序列,与EBV标准株及相关序列进行比对,绘制系统进化树,根据其特征性突变对基因变异进行分类,比较LMP1各变异类型在ENKTL和健康人群中分布的差异。结果:117例标本完成测序,共发现3种主要变异类型:China 1、China 2和Med-,其在ENKTL中的检出率分别为85.1%、8.5%和4.3%,在健康人群中的检出率分别为65.7%、5.7%和21.4%,另有1例(2.1%)ENKTL和5例(7.2%)健康人群为不同亚型的重组病毒株,LMP1亚型在2种人群中的分布差异具有统计学意义(P=0.022)。LMP1 N端Xho I位点缺失变异即Xho I(-)和C端30 bp缺失即del-LMP1在ENKTL中的检出率(95.7%和85.1%)高于健康人群(74.3%和67.1%),差异均有统计学意义(P=0.003和P=0.029)。结论:山东地区ENKTL中LMP1以China 1亚型、Xho I(-)和del-LMP1为主,带有3种变异型的EBV毒株可能与ENKTL的发生相关。OBJECTIVE： To characterize the sequence variations of Epstein-Barr virus（EBV）-encoded latent membrane protein I（LMPI） 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 LMPI 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 ofLMPI 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 LMP! 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, XhoI（-） and del-LMP1 were the major LMP1 subtypes in ENKTL and may associate with the susceptibility of ENKTL.

关 键 词：EB病毒 淋巴瘤 结外NK/T细胞 潜伏膜蛋白1 基因多态性 

分 类 号：R733[医药卫生—肿瘤]