EB病毒阳性的不同类型淋巴瘤组织中EBNA1多态性研究  

EBNA1 polymorphism in different types of lymphoma with positive Ep⁃stein-Barr virus

作　　者：徐海芹 冯征远 徐晓艳 孙亮亮 XU Hai-qin;FENG Zheng-yuan;XU Xiao-yan;SUN Liang-liang(Department of Pathology,Affiliated Hospital of Inner Mongolia Medical College,Hohhot 010059,China;Clinical Re-search Center,People's Hospital of Inner Mongolia Autonomous Region,Hohhot 010010,China;Clinical Laboratory,the Fourth Hospital of Inner Mongolia Autonomous Region,Hohhot 010010,China)

机构地区：[1]内蒙古医学院附属医院病理科,内蒙古呼和浩特010059 [2]内蒙古自治区人民医院医学检验科,内蒙古呼和浩特010010 [3]内蒙古自治区第四医院检验科,内蒙古呼和浩特010010

出　　处：《中国病理生理杂志》2021年第11期2057-2061,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81660393)。

摘　　要：目的:筛选前期研究中EB病毒(EBV)阳性的15例不同类型淋巴瘤病例,对这15例EBV阳性病例进行PCR扩增及EBV核抗原1(EBNA1)羧基端测序分析,观察是否存在突变热点AA487及AA466-527之间的变异。方法:采用PCR方法对EBV阳性病例进行EBNA1基因羧基端的扩增,并将扩增产物送公司进行测序分析。同时分析淋巴瘤患者EBV表达与预后的相关性。结果:本次实验成功扩增15例病例,进行EBNA1基因羧基端测序分析发现,15例标本中EBNA1羧基端均出现序列变异,其中以往报道过的突变有:错义突变AA487 A→V、499 D→E、502 T→N、524 T→I、528 I→V和533 L→I,无义突变为AA520密码子cat→ctc;本次研究新发现的突变有:错义突变AA462 G→E、466 G→R、AA487 A→L、492 S→C、502 T→N和524 T→I及无义突变AA466密码子gga→gaa、AA 480密码子aac→atc和AA 547密码子ccc→cct突变。几例非肿瘤细胞EBER阳性的淋巴瘤病例也均出现了与以往研究相同的共有突变;而肿瘤细胞EBER阳性的淋巴瘤样本中除了有部分共有突变外,均出现了非共有突变。结论:本组淋巴瘤病例中,除了有部分EBNA1基因羧基端的共有突变外,均出现了非共有突变,这与以往研究不同。AIM:To investigate the Epstein-Barr virus nuclear antigen 1(EBNA1) polymorphism in different types of lymphoma with positive Epstein-Barr virus(EBV).METHODS:Different types of lymphoma with positive EBV(n=15) were screened.The 15 EBV positive cases were analyzed by PCR amplification and EBNA1 carboxyl terminal sequencing to observe whether there was a mutation hot spot AA487 and the variation between AA466-527 s.PCR method was used to amplify the carboxy terminal of EBNA1 gene in EBV positive cases,and the amplified products were sent to the company for sequencing analysis.Simultaneous analysis of the correlation between EBV expression and prognosis in lymphoma was performed.RESULTS:In this experiment,15 cases were successfully amplified.The carboxy-end sequencing analysis of EBNA1 gene revealed that sequence variation occurred in the carboxy terminus of EBNA1 in 15 samples.Several cases of non-tumor cell EBER-positive lymphomas had the same common mutations as in previous reports.The newly discovered mutations in this study included missense mutations aa462 G→E,466 G→R,A A 487 A→L,492 S→C,502 tL→N and 524 t→I,nonsense mutations aa466 codon gga→gaa,A A 480 codon aac→atc and AA 547 codon ccc→cct.In addition to some common mutations,tumor cell EBER-positive lymphoma samples showed non-commonmutations.CONCLUSION:In this group of lymphoma cases,except for some common mutations at the carboxy terminus of the EBNA1 gene,non-common mutations occurred,which is different from previous studies.

关 键 词：淋巴瘤 EB病毒 EB病毒核抗原1 突变 

分 类 号：R733.4[医药卫生—肿瘤] R363.2[医药卫生—临床医学]