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鼻型和外周T细胞淋巴瘤中EB病毒的基因组分析:与地方性流行区鼻咽癌的比较

Genomic analysis of Epstein-Barr virus in nasal and peripheral T-cell lymphoma: a comparison with nasopharyngeal carcinoma in an endemic area.

作者信息

Wu S J, Lay J D, Chen C L, Chen J Y, Liu M Y, Su I J

机构信息

Graduate Institute of Pathology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan, Republic of China.

出版信息

J Med Virol. 1996 Dec;50(4):314-21. doi: 10.1002/(SICI)1096-9071(199612)50:4<314::AID-JMV6>3.0.CO;2-B.

DOI:10.1002/(SICI)1096-9071(199612)50:4<314::AID-JMV6>3.0.CO;2-B
PMID:8950688
Abstract

The Epstein-Barr virus (EBV) is prevalent in nasal and peripheral T-cell lymphoma (NPTL) in Taiwan, where nasopharyngeal carcinoma (NPC) is endemic. In order to understand the pathogenesis of these two malignancies in this endemic area, genomic analysis of EBV in NPTL with comparison to NPC is important. We investigated the EBV subtype (types A and B), BamH-I "f" variant, and the Xho-I site mutant of the latent membrane protein-1 (LMP-1) gene in 19 cases of EBV-associated NPTL and in 30 cases of NPC. EBV DNA from three patients with infectious mononucleosis (IM) was simultaneously studied as representative of normal healthy carriers. Similar to NPC and IM, the EBV in NPTL was found to belong to the type A strain in the majority (18 of 19) of cases by analyzing the 3' divergence of EBNA-2 genes. The extra restriction enzyme site in the BamHI-F region ("f" variant) of EBV DNA was frequently (15 of 30) demonstrated in NPC, but only rarely (1 of 19) was it detected in NPTL and IM (0 of 3). The Xho-I site mutant of the LMP-1 gene previously characterized in Chinese NPC also prevailed in NPTL and IM with an identical nucleotide sequence. No correlation exists between the EBV subtype and its variants. In conclusion, type A EBV is prevalent in Taiwanese NPTL, a finding much distinct from the dominance of type B virus in nonendemic European patients. The EBV genomes in NPTL are closely similar to those in IM or normal healthy carriers, but are distinct from NPC for the infrequency of the "f" variant. The prevalence of the LMP-1 mutant in this endemic region suggests that this EBV strain may confer a growth advantage role in the pathogenesis of these EBV-associated diseases. The rarity of the "f" variant in NPTL and its high frequency in NPC may explain the differential tumorigenesis of different EBV strains.

摘要

爱泼斯坦-巴尔病毒(EBV)在台湾的鼻型和外周T细胞淋巴瘤(NPTL)中普遍存在,而台湾是鼻咽癌(NPC)的高发地区。为了解该高发地区这两种恶性肿瘤的发病机制,对NPTL中的EBV进行基因组分析并与NPC进行比较很重要。我们研究了19例EBV相关NPTL和30例NPC中EBV的亚型(A和B型)、BamH-I “f” 变异体以及潜伏膜蛋白-1(LMP-1)基因的Xho-I位点突变。同时研究了3例传染性单核细胞增多症(IM)患者的EBV DNA作为正常健康携带者的代表。与NPC和IM相似,通过分析EBNA-2基因的3' 差异,发现大多数(19例中的18例)NPTL中的EBV属于A型毒株。EBV DNA的BamHI-F区域(“f” 变异体)中的额外限制性酶切位点在NPC中经常出现(30例中的15例),但在NPTL中很少检测到(19例中的1例),在IM中未检测到(3例中的0例)。先前在中国NPC中鉴定出的LMP-1基因的Xho-I位点突变在NPTL和IM中也以相同的核苷酸序列普遍存在。EBV亚型与其变异体之间不存在相关性。总之,A型EBV在台湾NPTL中普遍存在,这一发现与非高发地区欧洲患者中B型病毒占主导地位有很大不同。NPTL中的EBV基因组与IM或正常健康携带者中的EBV基因组非常相似,但与NPC不同,因为 “f” 变异体的频率较低。该高发地区LMP-1突变体的普遍存在表明,这种EBV毒株可能在这些EBV相关疾病的发病机制中发挥生长优势作用。NPTL中 “f” 变异体的罕见性及其在NPC中的高频率可能解释了不同EBV毒株的不同致瘤作用。

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