Faulty Genes Could Assist Cancer Fight

By Kevin Mayhood, The Columbus Dispatch, Ohio

Jan. 7–Overproductive genes that cause Down syndrome also suppress cancer tumors, according to researchers at Ohio State and Johns Hopkins universities.

“In Down syndrome, more than 150 genes are overexpressed,” said Roger H. Reeves, a physiology professor in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins. “This is one gene.”

One extra gene might not cause mental retardation, but it might have negative consequences that could be acceptable side effects in controlling a killer cancer, said Michael Ostrowski, co-director of Ohio State’s Comprehensive Cancer Center Program in Molecular Biology and Cancer Genetics. The gene, called Ets2, has been linked to the cause of some cancers in other studies. But in a study published last week in the journal Nature, the presence of an extra Ets2 gene suppressed colon cancer in mice.

The research supports studies that indicate people with Down syndrome have fewer cancers than the general population.

Nearly all people with Down syndrome have an extra copy of chromosome 21, the smallest of a human’s 23 pairs of chromosomes. Genes on the extra chromosome suppress mental development and create the characteristic facial features associated with the syndrome.

Reeves and Ostrowski implanted mice with 108 extra genes, including Ets2, from chromosome 21. These mice were mated with mice that carried a mutation that causes colon-cancer tumors.

Of the offspring that resulted, those that had the extra chromosome 21 genes had 44 percent fewer tumors. But these offspring also had arrested brain development and the facial features characteristic of Down syndrome.

The researchers next gave 33 extra genes, including Ets2, to another set of mice. Those mice had half the tumors of those not given the extra genes. The mice with the extra genes had some mental retardation and almost none of the Down syndrome facial features, the researchers said.

The researchers don’t know why fewer extra genes appear to be more effective.

One other test involved mice that had the same 32 other extra genes, plus one, two or three Ets2 genes. The offspring with the most Ets2 genes developed the fewest tumors.

Ostrowski said they will try to determine whether Ets2 without the other 32 extra genes suppresses tumors, and how and whether it carries problems.

The researchers said they also plan to test how the Ets2 gene affects other cancers.

“Chemotherapy used to treat cancer often causes other cancers later,” Ostrowski said. “The long-term goal is to use this to benefit everybody.”

kmayhood@dispatch.com

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