DNA methylation patterns in cancer: novel prognostic indicators?

DNA methylation is an epigenetic phenomenon influencing the normal function of DNA and its scaffolding proteins. Especially in cancer, aberrant methylation patterns may contribute to the disease process by the induction of point mutations, activation of inactive genes through hypomethylation of promoters, and transcriptional inactivation through a complex interplay with histone acetylation and other inhibitory mechanisms. Aberrant methylation patterns have been evaluated as tools in the management of patients with cancer. The predictive value, the therapeutic manipulation and the prognostic significance of aberrantly methylated gene loci have been tested in hematological as well as in solid neoplasias in adults and children. A seemingly insurmountable wealth of data has been generated, however, data on clinical associations are sometimes presented in an almost incautious fashion. Nevertheless, some genes like p15INK4B in myelodysplastic syndrome (MDS) and p16INK4A in some lung cancer subtypes have been shown to confer a certain prognosis. In selected cases the data have been confirmed by independent studies. Assays have been developed that can be used by almost any clinical laboratory (e.g. methylation-specific PCR) for the rapid and affordable screening of tumors for aberrant methylation. The study of aberrant methylation patterns has successfully entered the arena of relevant clinical applications. Importantly, methylation does not only hold the potential for being 'just another' biomarker, but also, as it can be reverted chemically, it is a phenomenon that holds great promise for therapeutic exploitation.