Epigenetics and cancer without genomic instability

Genomic instability is often considered a hallmark of cancer. However, it remains unclear whether chromosomal disorganization is most frequently a cause or a consequence of tumorigenesis. The fact that subsets of many cancers lack chromosomal or micro-satellite instability argues against the hypothesis that genomic instability plays an essential role in the initiation and maintenance of oncogenesis. Cancer-specific, epigenetically-based changes in gene expression caused by abnormalities in DNA methylation, in histone modifications, and in nucleosome positioning are gaining recognition as driving events in tumorigenesis. But are these changes merely a small piece of the oncogenesis puzzle or could they be the major component, or even sufficient for cancer? Here we discuss evidence that the progression of aggressive cancers can be driven by epigenetic events without genomic instability.