MOLECULAR ANALYSIS OF THE LMP (LATENT MEMBRANE-PROTEIN) ONCOGENE IN HODGKINS-DISEASE

Molecular analysis of the LMP (latent membrane protein) oncogene was p erformed in 21 Epstein-Barr virus (EBV) positive cases of Hodgkin's di sease (HD) with proven LMP gene expression. In each case, viral DNA of the LMP gene was assessed for polymorphism (deletions, insertions, mu tations) by polymerase chain reaction (PCR) amplification with selecte d primers. Specificity of the amplified targets was proven by internal oligonucleotide hybridisation and nested primer PCR. Homogeneity of t he 5' LMP gene region coding for the amino terminal, transmembrane, an d 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 preci sely localized by DNA sequencing. A particularly high frequency of DNA polymorphism (30% of cases) was found in the 3' untranslated LMP regi on. However, when analysing the LMP gene in seven benign conditions, n o DNA polymorphism was found. These data suggest conservation of oncog enic LMP regions coding for the protein domains known to be associated with transforming capacities and immunogenic functions. They also sho w a considerable genomic heterogeneity of the coding region for the in tracytoplasmic domain and the 3' untranslated mRNA region. This LMP DN A polymorphism identified within a localized (Swiss) population suffer ing from HD is unexpected. Its eventual clinical significance remains to be determined.