Much of the current hype in epigenetics stems from the recognition of its role in human cancer. Yet, intriguingly, the first epigenetic change in human tumors—global genomic DNA hypomethylation—was reported way back in the early 1980s, at about the same time the first genetic mutation in an oncogene was discovered.1 So why the delay in recognizing the importance of epigenetics in cancer?
In the 1980s epigenetics was a fledgling discipline, hampered by methodological limitations, while genetic knowledge of cancer was expanding exponentially. By the mid-1990s however, classical tumor suppressor genes, such as p16INK4a, hMLH1, and VHL,2 were shown to undergo a specific epigenetic hit (the inactivation of gene expression by CpG island hypermethylation), resulting in a major acceleration in the field. We now know that so-called “epigenetic changes” explain many hallmark features of malignant disease: these genes are deregulated not at the DNA level, but at the complexly packaged chromatin ...