Chen Y Y, Chang K L, Chen W G, Shibata D, Hayashi K, Weiss L M
City of Hope National Medical Center, Duarte, California 91010-0269, USA.
Lab Invest. 1998 Jul;78(7):877-82.
We examined Epstein-Barr virus (EBV)-associated nuclear antigen-1 (EBNA-1) gene carboxy (C)-terminal deletions occurring in gastric carcinoma and noncarcinoma tissues from two different ethnic populations. Previously reported EBNA-1 C-terminal region amino acid sequence variations include five subtypes based on the amino acid at codon 487: Prototype (P)-ala, which is found in the B95.8-derived prototype virus; P-thr; Variant (V)-pro; V-leu; and V-val. Using polymerase chain reaction to amplify fragments of the EBNA-1 gene, followed by gene sequencing, we identified a single EBNA-1 gene sequence variant (V-val') in all 25 cases of known EBV-positive gastric carcinoma and all 8 cases of known EBV-positive reactive follicular hyperplasia from Japan. All 17 cases of known EBV-positive American gastric carcinomas had a single EBNA-1 gene sequence, including 3 P-ala or P-ala variants, 9 P-thr, 4 V-leu or V-leu variants, and 1 V-val'. All 11 cases of American reactive lymphoid tissue also had a single EBNA-1 gene sequence, including 2 P-ala variants, 5 P-thr or P-thr variants, and 4 V-leu. Variant EBNA-1 sequences were more common in both carcinoma and non-neoplastic tissues than the prototype sequence, whether from Japan or America. The EBNA-1 gene sequences found in the two ethnic populations differed, suggesting that variation in EBNA-1 gene sequence is due to polymorphisms present within pre-existing viral strains prevalent within various ethnic populations. The EBNA-1 gene sequences in reactive tissues were similar to those in malignant tissues from the same ethnic population, suggesting that the differences in EBNA-1 gene sequences do not result from mutation occurring during neoplastic transformation and that there may not be a selective cell tropism for different EBNA-1 proteins, as previously suggested.
我们检测了来自两个不同种族人群的胃癌组织和非癌组织中发生的爱泼斯坦-巴尔病毒（EBV）相关核抗原1（EBNA-1）基因羧基（C）末端缺失情况。先前报道的EBNA-1 C末端区域氨基酸序列变异包括基于密码子487处氨基酸划分的五个亚型：原型（P）-丙氨酸，存在于源自B95.8的原型病毒中；P-苏氨酸；变异型（V）-脯氨酸；V-亮氨酸；以及V-缬氨酸。我们采用聚合酶链反应扩增EBNA-1基因片段，随后进行基因测序，在来自日本的所有25例已知EBV阳性胃癌病例以及所有8例已知EBV阳性反应性滤泡增生病例中均鉴定出单一的EBNA-1基因序列变异（V-缬氨酸'）。所有17例已知EBV阳性的美国胃癌病例均具有单一的EBNA-1基因序列，其中包括3例P-丙氨酸或P-丙氨酸变异型、9例P-苏氨酸、4例V-亮氨酸或V-亮氨酸变异型以及1例V-缬氨酸'。所有11例美国反应性淋巴组织病例也均具有单一的EBNA-1基因序列，其中包括2例P-丙氨酸变异型、5例P-苏氨酸或P-苏氨酸变异型以及4例V-亮氨酸。无论是来自日本还是美国，变异型EBNA-1序列在癌组织和非肿瘤组织中均比原型序列更为常见。在这两个种族人群中发现的EBNA-1基因序列存在差异，这表明EBNA-1基因序列变异是由于各不同种族人群中普遍存在的原有病毒株内的多态性所致。反应性组织中的EBNA-1基因序列与来自同一种族人群的恶性组织中的序列相似，这表明EBNA-1基因序列差异并非由肿瘤转化过程中发生的突变导致，并且可能不存在如先前所认为的针对不同EBNA-1蛋白的选择性细胞嗜性。
