The cancer-causing potential of certain genes may depend on whether other genes are inherited from mom or dad, concludes a study published online this week in the Proceedings of the National Academy of Sciences.

In the name of the father. Without a maternal imprint on certain genes, paternal imprinting seems to accelerate cancer in embryonic tumors such as this. CREDIT: L. HERNANDEZ/NCI

In addition to inheriting genes, offspring also inherit a pattern of chemical modifications to the DNA of certain genes. The modifications are fixed before fertilization--some by the mother, some by the father--switching so-called imprinted genes either on or off during development. Scientists knew that alterations to the imprinted pattern can contribute to tumor formation by loosening controls on cell growth. Wondering if maternally and paternally imprinted genes play different roles in cancer, a team led by Colin Stewart, a cell biologist at the National Cancer Institute in Frederick, Maryland, devised a new cloning technique to create mouse embryos carrying exclusively maternal or paternal imprinting.

The researchers used the technique to clone mice carrying one of three mutations that kick-start cancer at the embryonic stage. The team compared the mutations' malignancy by culturing the embryos and injecting them under the skin of test mice. Stewart was prepared for subtle differences, but the effects of maternal and paternal imprinting were drastically different: Paternally imprinted embryos formed aggressive, fast-growing tumors, while the maternally imprinted embryos slowed down and died off harmlessly. "We were very surprised" by the difference between the effects of imprinting from the two sexes, says Stewart. The finding provides a first step toward understanding how factors other than mutation cause cancer, says Stewart, and could point the way toward treating cancers by manipulating genetic imprinting--a trick scientists have yet to master.

"This is a very original and convincing study," says Tim Bestor, a cell biologist at Columbia University in New York City. Bestor suggests that the main importance of these results will be for childhood cancers in which genetic imprinting is thought to be a root cause.

--JOHN BOHANNON

Related sites
Stewart's home page
Bestor's home page