New view of cancer: 'Epigenetic' changes come before mutations

A Johns Hopkins researcher, with colleagues in Sweden and at the Fred Hutchinson Cancer Research Center, suggests that the traditional view of cancer as a group of diseases with markedly different biological properties arising from a series of alterations within a cell's nuclear DNA may have to give way to a more complicated view. In the January issue of Nature Reviews Genetics, available online Dec. 21, he and his colleagues suggest that cancers instead begin with "epigenetic" alterations to stem cells.

"We're not contradicting the view that genetic changes occur in the development of cancers, but there also are epigenetic changes and those come first," says lead author Andrew Feinberg, M.D., M.P.H., King Fahd Professor of Medicine and director of the Center for Epigenetics in Common Human Disease at Johns Hopkins.

Cells affected by epigenetic changes look normal under a microscope at low levels of resolution, Feinberg says, "but if you look carefully at the genome, you find there are subtle changes." By tracking these changes, he suggests, doctors potentially could treat people before tumors develop in much the same way as cardiologists prescribe cholesterol-lowering drugs to help prevent heart disease.

Epigenetic changes -- those that don't affect the gene's sequence of DNA but change the gene in other ways -- influence a wide variety of human diseases, including cancer, birth defects and psychiatric conditions. Epigenetic alterations include the turning off or quieting of genes that normally suppress cancer and the turning on of oncogenes to produce proteins that set off malignant behavior.

Epigenetic changes are found in normal cells of patients with cancer and are associated with cancer risk, Feinberg notes.

As one example, in a study published in the Feb. 24, 2005, online version of Science, Feinberg and colleagues in the United States, Sweden and Japan reported that mice engineered to have a double dose of insulin-

Contact: Joanna Downer
Johns Hopkins Medical Institutions

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