Methylation matters

DNA methylation is not just for basic scientists any more. There is a growi ng awareness in the medical field that having the correct pattern of genomi c methylation is essential for healthy cells and organs. If methylation pat terns are not properly established or maintained, disorders as diverse as m ental retardation, immune deficiency, and sporadic or inherited cancers may follow. Through inappropriate silencing of growth regulating genes and sim ultaneous destabilisation of whole chromosomes, methylation defects help cr eate a chaotic state from which cancer cells evolve. Methylation defects ar e present in cells before the onset of obvious malignancy and therefore can not be explained simply as a consequence of a deregulated cancer cell. Rese archers are now able to detect with exquisite sensitivity the cells harbour ing methylation defects, sometimes months or years before the time when can cer is clinically detectable. Furthermore, aberrant methylation of specific genes has been directly linked with the tumour response to chemotherapy an d patient survival. Advances in our ability to observe the methylation stat us of the entire cancer cell genome have led us to the unmistakable conclus ion that methylation abnormalities are far more prevalent than expected. Th is methylomics approach permits the integration of an ever growing repertoi re of methylation defects with the genetic alterations catalogued from tumo urs over the past two decades. Here we discuss the current knowledge of DNA methylation in normal cells and disease states, and how this relates direc tly to our current understanding of the mechanisms by which tumours arise.