We have investigated the consequences of foreign DNA insertions into the genomes of mammalian cells in transgenic cell lines, in adenovirus type 12 (Ad12)-transformed cells, in Ad12-induced tumor cells or in transgenic mice. We have reported previously on the de novo methylation of integrated foreign genomes and on extensive changes in cellular patterns of DNA methylation upon foreign DNA insertion. These studies have been extended and several independent methods have been applied to document these alterations in cellular DNA methylation and gene expression patterns in transgenic cell lines and in transgenic mice. These data are relevant for the mechanism of (viral) oncogenesis and for the interpretation of data gathered in experiments with transgenic animals.