POINT MUTATIONS AND NUCLEOTIDE INSERTIONS IN THE MDM2 ZINC-FINGER STRUCTURE OF HUMAN TUMORS

This study investigates the human oncoprotein MDM2, which interferes w ith regulation of cell division and apoptosis. Fifteen mixed-type foll icular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular car cinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, ost eoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 ex pression and MDM2 gene mutation by reverse transcriptase-polymerase ch ain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence an alysis, Two follicular lymphomas, three leukaemias, both hepatocellula r carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene, These samples lacked amplified MDM2 genes and car ried mis-sense, non-sense and frame-shift mutations in a zinc finger r egion of MDM2, altering tile amino acid sequence or causing premature termination of transcription, The mis-sense mutations were found in tu mour cells that showed significant accumulation of MDM2 and lack of nu clear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins, The mutations may affect the biologica l properties of MDM2 proteins. (C) 1997 by John Wiley & Sons, Ltd.