Knecht H, Bachmann E, Joske D J, Sahli R, Eméry-Goodman A, Casanova J L, Zilić M, Bachmann F, Odermatt B F
Department of Internal Medicine, CHUV University Hospital, Lausanne, Switzerland.
Leukemia. 1993 Apr;7(4):580-5.
Molecular analysis of the LMP (latent membrane protein) oncogene was performed in 21 Epstein-Barr virus (EBV) positive cases of Hodgkin's disease (HD) with proven LMP gene expression. In each case, viral DNA of the LMP gene was assessed for polymorphism (deletions, insertions, mutations) by polymerase chain reaction (PCR) amplification with selected primers. Specificity of the amplified targets was proven by internal oligonucleotide hybridisation and nested primer PCR. Homogeneity of the 5' LMP gene region coding for the amino terminal, transmembrane, and short extracytoplasmic domains of the protein was identified in all cases. However, deletions or insertions of small DNA sequences within the coding region for the intracytoplasmic LMP domain were observed in about 20% of cases. In one of them, a 30-base-pair deletion was precisely localized by DNA sequencing. A particularly high frequency of DNA polymorphism (30% of cases) was found in the 3' untranslated LMP region. However, when analysing the LMP gene in seven benign conditions, no DNA polymorphism was found. These data suggest conservation of oncogenic LMP regions coding for the protein domains known to be associated with transforming capacities and immunogenic functions. They also show a considerable genomic heterogeneity of the coding region for the intracytoplasmic domain and the 3' untranslated mRNA region. This LMP DNA polymorphism identified within a localized (Swiss) population suffering from HD is unexpected. Its eventual clinical significance remains to be determined.
对21例已证实有LMP基因表达的霍奇金病（HD）的爱泼斯坦-巴尔病毒（EBV）阳性病例进行了LMP（潜伏膜蛋白）癌基因的分子分析。在每例病例中，通过用选定引物进行聚合酶链反应（PCR）扩增，评估LMP基因的病毒DNA的多态性（缺失、插入、突变）。通过内部寡核苷酸杂交和巢式引物PCR证实扩增靶标的特异性。在所有病例中均鉴定出编码该蛋白氨基末端、跨膜和短胞外结构域的5'LMP基因区域的同质性。然而，在约20%的病例中观察到胞质内LMP结构域编码区域内小DNA序列的缺失或插入。其中1例通过DNA测序精确确定了一个30个碱基对的缺失。在3'非翻译LMP区域发现DNA多态性的频率特别高（30%的病例）。然而，在分析7种良性疾病中的LMP基因时，未发现DNA多态性。这些数据表明，编码已知与转化能力和免疫原性功能相关的蛋白结构域的致癌LMP区域具有保守性。它们还显示出胞质内结构域和3'非翻译mRNA区域编码区域存在相当大的基因组异质性。在一个患HD的局部（瑞士）人群中鉴定出的这种LMP DNA多态性是出乎意料的。其最终的临床意义仍有待确定。
