How Randomness Helps Cancer Cells Thrive

In a research effort that merged genetics, physics and information theory, a team at the schools of medicine and engineering at The Johns Hopkins University has added significantly to evidence that large regions of the human genome have built-in variability in reversible epigenetic modifications made to their DNA.

In a report on the research published March 27 in Nature Genetics, the team says the findings also suggest that such epigenetic variability is a major factor in the ability of cancer cells to proliferate, adapt and metastasize.

“These results suggest that biology is not as deterministic as many scientists think,” says Andrew Feinberg, M.D., M.P.H., the King Fahd Professor of Medicine, Oncology, and Molecular Biology and Genetics at the Johns Hopkins University School of Medicine and director of the Center for Epigenetics in the Institute for Basic Biomedical Sciences. “If so, they could have major implications for how we treat cancer and other aging-related diseases.”

Epigenetic modifications, achieved along the genome by the chemical attachment of methyl molecules, or tags, to DNA, are reversible changes that alter which genes are turned on or off in a given cell without actually altering the DNA sequence of the cell. Such changes enable a complex organism, like a human, to have a wide range of different tissues that all still have the exact same genetic template.

However, in some studies with laboratory mice, Feinberg had observed that these epigenetic tags varied considerably among the mice even when comparing the same type of tissue in animals that have been living in the exact same conditions. “These weren’t minor differences, and some very important genes were involved,” Feinberg says.

Feinberg, who is also a Bloomberg Distinguished Professor of Engineering and Public Health at The Johns Hopkins University, suspected that this variation might be an adaptive feature by which built-in epigenetic randomness would give some cells an advantage in rapidly changing environments.

To find out if that was the case, he teamed up with John Goutsias, Ph.D., professor of electrical and computer engineering at the Johns Hopkins Whiting School of Engineering, to find a way to measure this controlled type of randomness, scientifically termed epigenetic stochasticity, by using the information-theoretic concept of Shannon entropy.

Excerpted from Johns Hopkins Medicine.