Hirose Y, Masaki Y, Kurose N
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
Int J Hematol. 2000 Aug;72(2):210-5.
The association of Epstein-Barr virus (EBV) with various lymphoid malignancies has been reported. The precise pathogenesis of EBV in malignancies has not yet been elucidated. Latent membrane protein-1 (LMP-1) and Epstein-Barr nuclear antigen-2 (EBNA-2) genes are suspected to be tumorigenic genes. Previous studies suggest that a deletion within the LMP-1 gene may increase the oncogenic potential of EBV. In this study, we analyzed the sequence within the carboxy terminal end of the LMP-1 gene in paraffin-embedded specimens from T-cell lymphomas, Hodgkin's disease (HD), and the buffy coat of peripheral blood from healthy individuals in Japan. Polymerase chain reaction (PCR) was performed using primers spanning the carboxy terminal region of the LMP-1 gene, and sequence analysis was performed to show the exact location of the deletion. The PCR product of the Raji cell line was 161 base pairs (bp), and the LMP-1 gene with deletion was 30 bp shorter in a direct sequence of PCR products. The 30-bp deletion was located in position 168285-168256 of the Raji cell. A deletion within the LMP-1 gene was found in 4 of 25 cases (16%) of EBV-positive T-cell lymphomas, 4 of 10 cases (40%) of EBV-positive HD cases, and 2 of 13 specimens (15%) with amplified PCR products from 49 healthy individuals. The incidence of the 30-bp deletion within the LMP-1 gene in HD was comparable to that of subjects in the United States and Brazil, but the deletion was not found in a high proportion of EBV-positive T-cell lymphoid malignancies. No statistical significance was found regarding the clinical outcome between patients with a deletion within the LMP-1 gene and patients with wild-type LMP. This deletion cannot be considered as simply causing the pathogenesis of EBV-associated lymphoid malignancies in Japan.
已有报道称爱泼斯坦-巴尔病毒（EBV）与多种淋巴恶性肿瘤有关。EBV在恶性肿瘤中的精确发病机制尚未阐明。潜伏膜蛋白-1（LMP-1）和爱泼斯坦-巴尔核抗原-2（EBNA-2）基因被怀疑是致瘤基因。先前的研究表明，LMP-1基因内的缺失可能会增加EBV的致癌潜力。在本研究中，我们分析了来自日本T细胞淋巴瘤、霍奇金病（HD）石蜡包埋标本以及健康个体外周血 Buffy 层中LMP-1基因羧基末端的序列。使用跨越LMP-1基因羧基末端区域的引物进行聚合酶链反应（PCR），并进行序列分析以显示缺失的确切位置。Raji细胞系的PCR产物为161个碱基对（bp），在PCR产物直接测序中，缺失的LMP-1基因短30 bp。30 bp的缺失位于Raji细胞的168285 - 168256位。在25例EBV阳性T细胞淋巴瘤中的4例（16%）、10例EBV阳性HD病例中的4例（40%）以及49名健康个体中13份有扩增PCR产物的标本中的2份（15%）发现了LMP-1基因内的缺失。HD中LMP-1基因30 bp缺失的发生率与美国和巴西的受试者相当，但在高比例的EBV阳性T细胞淋巴恶性肿瘤中未发现该缺失。LMP-1基因有缺失的患者与野生型LMP患者之间的临床结局未发现统计学意义。在日本，这种缺失不能被简单地认为是导致EBV相关淋巴恶性肿瘤发病机制的原因。
