Extra Gene May Explain Why Down's Syndrome Patients Less Susceptible to Cancer

Extra Gene May Explain Why Down's Syndrome Patients Less Susceptible to Cancer

May 21, 2009 4:15 PM

(SALT LAKE CITY) --A study by a group of national and international researchers has identified, in part, why Down's syndrome patients rarely get most types of cancer: an extra copy of a gene they carry helps suppress tumor growth by stopping blood vessel formation. 

In a study in Nature online this week, researchers including Julie R. Korenberg Ph.D., M.D., USTAR professor of pediatric genetics at the University of Utah School of Medicine and an investigator with the University's Brain Institute, showed that the extra expression of a gene called DSCR1 appeared to be sufficient to stop blood vessel formation that helps tumors grow. DSCR1 influences this process by regulating a protein that suppresses vascular endothelial growth factor (VEGF), a substance critical for blood vessel formation or angiogenesis.

The finding means that drugs might be developed to stop blood vessel formation in cancerous tumors, thereby killing them.

"There is a genetic pathway we haven't known about that protects against cancer," said Korenberg, a co-author on the study. "By having, in effect, 50 percent more of this gene (DSCR1), Down syndrome patients see a significant reduction in solid tumor incidence."

Humans typically carry 46 chromosomes and two copies of every gene. But those with Down's syndrome have an extra copy of chromosome 21, meaning they carry three copies of all 231 genes found on that chromosome, including DSCR1.

One of DSCR1's roles is to encode, or switch on and off, a protein that activates VEGF to form blood vessels in human development. But even when body cellular processes go awry in the unregulated growth that forms tumors, blood vessels are used to supply the nutrients tumors need to grow.

Clinicians and researchers long have observed that Down's syndrome patients have a far lower incidence of breast, lung, colon, and other solid-tumor cancers. In the Nature study, the researchers transplanted lung and melanoma cancer cells into two groups of mice: one that carried the extra copy of DSCR1 and a control group that didn't have the extra gene. They observed considerable tumor suppression and less blood vessel formation in the mice with the extra gene copy, compared with the control group, leading them to suspect that DSCR1 plays the same role in people with Down's syndrome and that increased dosage of the gene, perhaps in a drug, might suppress blood vessel growth.

Along with the observations in mice, the study also is based in observed biological processes in people with Down syndrome, and that opens a window on what happens with adult disease, according to Korenberg, a leading researcher in Down's and Williams syndromes recruited to Utah as part of the Utah Science and Technology Research Initiative (USTAR).

"This study is based in human processes and, therefore, may provide more confidence that clinical scientists can develop effective new treatments for human cancer from its findings," she said. "At the Brain Institute, we think it's important to do the basic research, but at the same time, we always keep on eye on what will be of greatest use to the clinician. We have a constant focus on what ultimately will improve human health."

The study was led by Sandra Ryeom, Ph.D., instructor in surgery at Harvard Medical School and Children's Hospital, Boston, and Kwan-Hyuck Baek, Ph.D., research fellow in surgery at Children's Hospital, Boston.

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