Global and gene-specific methylation patterns in cancer:: Aspects of tumor biology and clinical potential

Heritable alterations of DNA that do not affect the base pair sequence itself but nevertheless regulate the predetermined activity of genes are referred to as epigenetic. Epigenetic mechanisms comprise diverse phenomena including stable feedback loops, nu ear compartmentalization, differential replication timing, heritable chromatin structures, and, foremost, DNA cytosine methylation (1-3). DNA cytosine methylation has recently gained major attention in the field of basic molecular biology as well as in studies of human diseases including cancer. Changes in DNA methylation patterns in human malignancies have been shown to contribute to carcinogenesis in multiple ways. Both hypo- and hypermethylation events have been described in various neoplasias leading to chromosomal instability and transcriptional gene silencing. DNA methylation research has entered the clinical arena and methylation patterns have become a major focus of clinicians seeking novel prognostic factors and therapeutic targets. The following mini-review covers aspects of the basic molecular biology of DNA methylation and summarizes its importance in human cancers. (C) 2002 Elsevier Science (USA).