Despite the completion of the Human Genome Project, we are still far from 
understanding the molecular events underlying epigenetic change in cancer. 
Cancer is a disease of the DNA with both genetic and epigenetic changes 
contributing to changes in gene expression. Epigenetics involves the interplay 
between DNA methylation, histone modifications and expression of non-coding RNAs 
in the regulation of gene transcription. We now know that tumour suppressor 
genes, with CpG island-associated promoters, are commonly hypermethylated and 
silenced in cancer, but we do not understood what triggers this process or when 
it occurs during carcinogenesis. Epigenetic gene silencing has always been 
envisaged as a local event silencing discrete genes, but recent data now 
indicates that large regions of chromosomes can be co-coordinately suppressed; a 
process termed long range epigenetic silencing (LRES). LRES can span megabases 
of DNA and involves broad heterochromatin formation accompanied by 
hypermethylation of clusters of contiguous CpG islands within the region. It is 
not clear if LRES is initiated by one critical gene target that spreads and 
conscripts innocent bystanders, analogous to large genetic deletions or if 
coordinate silencing of multiple genes is important in carcinogenesis? Over the 
next decade with the exciting new genomic approaches to epigenome analysis and 
the initiation of a Human Epigenome Project, we will understand more about the 
interplay between DNA methylation and chromatin modifications and the expression 
of non-coding RNAs, promising a new range of molecular diagnostic cancer markers 
and molecular targets for cancer epigenetic therapy.