DNA methylation in neoplasia

It is now well established that epigenetic mechanisms play a pivotal role in neoplasia. Genome-wide and gene specific DNA methylation changes are associated with a wide variety of neoplasms and many of these changes have been shown to be an early event in neoplastic change (1). Methyltransferase (MTase), the enzyme lesponsible for catalysis of DNA methylation and therefore gene expression, exhibits an increased expression to levels as high as several hundred-fold above normal with in vitro transformation and neoplastic transformation in vivo (2). As hypomethylation has been associated with increased gene expression, the authors hypothesised that the MTase gene will be hypomethylated in neoplasms. DNA was digested with the isoschizomers Mspl and Hpall and analysed by Southern blotting using species-specific probes for the MTase gene. Two human glioblastoma multiforme, 1 peripheral nerve sheath tumour, a number of murine sarcomas and 1 murine adenocarcinoma included in the study exhibited hypomethylation of the MTase gene when compared with the normal pattern of methylation. Human tumours xenografted into nude mice have been reported to have variable effects on host cells forming the supporting stroma, in a small number of cases causing the neoplastic transformation of these cells (3). For this reason, methylation of the MTase gene in murine stroma was also examined in this study and revealed variable changes in murine stroma under the influence of human elioblastoma multiforme and peripheral nerve sheath tumours.