Sure, genes get mutated in cancers, but the epigenome gets messed-up too. In fact, two researchers argue in a recent review that a “dysregulated epigenome” that’s too plastic and flexible could itself lead to cancer.
Andrew Feinberg and Winston Timp, both from the Center for Epigenetics at the Johns Hopkins School of Medicine, wrote the review.
“We haven’t paid enough attention to natural selection in the evolution of cancer,” says Feinberg. “We argue here that cancer has, as a central common feature, a dysregulated epigenome that allows for selection of the cancer cell at the expense of the host, and that many of the hallmarks of cancer follow from that principle.”
They summarize the evidence, which comes from their and other researchers’ labs. Here are some of the topics they touch on:
- Large epigenetic structures. LOCKs (large organized heterochromatin K[lysine] modification) and hypomethylated blocks overlap in some cancers. Lots of genes get variably expressed in hypomethylated blocks, and this heterogeneity could be important in cancer. The blocks also could contribute to gene mutations.
- Small epigenetic structures. CGIs and shores, loss of CGI boundary stability, and small chromatin domains, like individual nucleosomes, also play roles in cancer.
- Mutated epigenetic modifiers. These could explain how some DNA mutations lead to cancer.
Feinberg and TImp point out in the review that their model of epigenetic variability in cancer could lead to new markers for use in new diagnostic tests, as well as new drug targets for therapies.
Find the latest on epigenomics and cancer at Nature Reviews Cancer, July 2013.