Sequence analysis of Epstein-Barr virus EBNA-2 gene coding amino acid 148-487 in nasopharyngeal and gastric carcinomas.
Sequence analysis of Epstein-Barr virus EBNA-2 gene coding amino acid 148-487 in nasopharyngeal and gastric carcinomas.
复制标题
鼻咽癌和胃癌中EB病毒EBNA-2基因编码氨基酸148-487的序列分析
DOI：
10.1186/1743-422x-9-49
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发表时间：
2012-02-21
期刊：
影响因子：
4.8
通讯作者：
Luo B
中科院分区：
文献类型：
--
作者：
Wang X;Wang Y;Wu G;Chao Y;Sun Z;Luo B
研究背景EB病毒（Epstein-Barr virus，EBV）核抗原2（Nuclear antigen 2，EBNA-2）在体外B细胞增殖转化中起关键作用。EBNA-2基因的编码区氨基酸（aa）148-487的序列测定在中国北方25例EBV相关胃癌（EBVaGCs）、56例鼻咽癌（NPC）和32例健康人咽拭子（TW）中进行。在所有样本中检测到三种变异（g48991 t，c48998 a，t49613 a）（113/113，100%）。根据EBNA-2基因294 Q、357 K和358 G三个氨基酸的缺失情况，EBNA-2可分为E2-A、E2-B、E2-C和E2-D四种亚型。E2-A亚型检出率为49.6%（56/113），E2-C亚型检出率为33.6%（38/113）。E2-A亚型在EBVaGCs中检出较多，E2-D亚型仅在NPC中检出。EBNA-2基因功能区变异分析：EBNA-2基因羧基端的E438 L和E476 G、P484 H和I486 T为NPC中的优势基因型。结论E2-A和E2-C亚型是中国北方鼻咽癌EBNA-2基因的优势基因型。E2-D亚型可能与鼻咽癌的发生有关。NPC分离株在功能区的突变频率高于其他两组。
BackgroundThe Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) plays a key role in the B-cell growth transformation by initiating and maintaining the proliferation of infected B-cell upon EBV infection in vitro. Most studies about EBNA-2 have focused on its functions yet little is known for its intertypic polymorphisms.ResultsCoding region for amino acid (aa) 148-487 of the EBNA-2 gene was sequenced in 25 EBV-associated gastric carcinomas (EBVaGCs), 56 nasopharyngeal carcinomas (NPCs) and 32 throat washings (TWs) from healthy donors in Northern China. Three variations (g48991t, c48998a, t49613a) were detected in all of the samples (113/113, 100%). EBNA-2 could be classified into four distinct subtypes: E2-A, E2-B, E2-C and E2-D based on the deletion status of three aa (294Q, 357K and 358G). Subtypes E2-A and E2-C were detected in 56/113 (49.6%), 38/113 (33.6%) samples, respectively. E2-A was observed more in EBVaGCs samples and subtype E2-D was only detected in the NPC samples. Variation analysis in EBNA-2 functional domains: the TAD residue (I438L) and the NLS residues (E476G, P484H and I486T) were only detected in NPC samples which located in the carboxyl terminus of EBNA-2 gene.ConclusionsThe subtypes E2-A and E2-C were the dominant genotypes of the EBNA-2 gene in Northern China. The subtype E2-D may be associated with the tumorigenesis of NPC. The NPC isolates were prone harbor to more mutations than the other two groups in the functional domains.