Loss of chromosomal integrity in human mammary epithelial cells subsequentto escape from senescence

The genomic changes that foster cancer can be either genetic or epigenetic in nature. Early studies focused on genetic changes and how mutational even ts contribute to changes in gene expression. These point mutations, deletio ns and amplifications are known to activate oncogenes and inactivate tumor suppressor genes. More recently, multiple epigenetic changes that can have a profound effect on carcinogenesis have been identified. These epigenetic events, such as the methylation of promoter sequences in genes, are under a ctive investigation. In this review we will describe a methylation event th at occurs during the propagation of human mammary epithelial cells (HMEC)(4 ) in culture and detail the accompanying genetic alterations that have been observed.