中文摘要：

目的探讨青岛地区EB病毒（EBV）阳性淋巴瘤组织中EBNA2编码基因变异规律及其基因多态性的意义。方法用原位杂交技术筛选出EBV阳性淋巴瘤76例,采用聚合酶链反应（PCR）结合DNA测序技术检测淋巴瘤组织中EBNA2基因148~487位氨基酸编码序列多态性,并与EBV阳性健康人咽漱液进行比较。结果根据序列变异特点,EBV阳性淋巴瘤组织检测到4种EBNA2基因型,其中B95-8型4例（5.2%）,E2-1型40例（52.6%）,E2-2型22例（29.0%）,E2-3型10例（13.2%）。4种亚型在EBV阳性淋巴瘤和咽漱液标本中的分布差异有显著性（P=0.047）,但在不同病理类型淋巴瘤中的分布差异无显著性（P〉0.05）。所有咽漱液及约95%（72/76）的淋巴瘤标本中观察到R163M、165gtc→gta和370cct→cca等3个共有突变。功能区分析显示,EBV阳性淋巴瘤标本在反式激活区、自身聚合区及核定位信号区均检测到突变,包括错义突变、氨基酸缺失和插入等;而咽漱液标本仅在自身聚合区及核定位信号区检测到少量突变;E2-3亚型淋巴瘤标本检测到2个抗原表位发生氨基酸突变。结论 E2-1和E2-2亚型是青岛地区EBNA2基因的主要亚型,EBNA2基因多态性可能与淋巴瘤的发生有关;R163M、165gtc→gta和370cct→cca是青岛地区EBV阳性淋巴瘤的特征性突变;EBNA2基因不同功能区的某些突变可能对其功能产生影响。

英文摘要：

Objective To explore the mutation law of EBNA2 gene in EBV-positive lymphoma and its significance of gene polymorphism. Methods Employing in situ hybridization technique, 76 EBV-positive lymphomas were picket out. Encoding sequence polymorphism of EBNA2 gene in lymphoma tissues was detected using combined PCR and DNA sequence technique, the findings were compared with throat washing samples of EBV-positive healthy donors. Results According to the characteristics of sequence variation, four EBNA2 genotypes-B95-8 （4/76,5.2X）, E2-1 （40/76,52.6%）, E2 2 （22/76,29.0%） and E2-3 （10/76,13.2%）-were detected in EBV-positive lymphoma tissues. The differences in distribution of EBV-positive lymphoma tis sues and throat washing samples were significant （P =0.047）, but the differences in different pathological types were not significant （P〉0.05）. Three common mutations-R163M, 165gtc→gta and 370cct→cca -were detected in all throat washing samples and 95% （72/76） of iymphoma specimens. Functional analysis showed that there were some mutations, including missense mutation, amino acid （AA） deletion and AA insertion, in transactivation domain （TAD）, self-association domain and nuclear localization signals （NLS） domain in lymphoma samples, while in throat washing samples only few mutations in self-association domain and NLS domain were found. AA interchange including two epitopes was detected in lymphoma isolates which belong to type E2 3. Conclusion Type E2 1 and E2-2 are main subtypes of EBNA2 in Qingdao area. Polymorphism of EBNA2 is probably associated with the pathogenesis of lymphoma. R163M, 165gtc→gta and 370eet→cca are characteristic mutations of EBV-positive lymphoma in Qingdao area. In functional domains, some mutations may influence the function of EBNA2.