For decades scientists have known that people with Down syndrome, who have an extra copy of chromosome 21, get certain types of cancer at dramatically lower rates than normal. Now, partly by using stem cells derived from the skin of an individual with Down syndrome, researchers at Children's Hospital Boston have pinpointed the gene that appears to underlie the cancer-protective effect.

The researchers say the results of their study, which were published today in Nature, may point to a promising new target for future cancer treatments. And according to stem-cell biologists, the work also highlights a growing trend in the field: harnessing disease-specific stem cells not as therapies but rather as models for understanding particular genetic disorders.

Stem cells "can be useful not simply because you take them and transplant them," says Evan Snyder, director of the stem cells and regenerative medicine program at the Burnham Institute for Medical Research in San Diego. "They are useful as models of disease that reveal other kinds of therapies." Snyder was not involved in the new study.

The late Judah Folkman, a cancer researcher renowned for pioneering the notion that blocking angiogenesis--the growth of new blood vessels--can prevent tumors from thriving, hypothesized that the lower cancer rates associated with Down syndrome might be traced to anti-angiogenesis genes on the 21st chromosome. So Sandra Ryeom, a member of the Folkman Laboratory in the Vascular Biology Program at Children's Hospital, zeroed in on a region on chromosome 21 known to encode a regulator of blood vessel growth called DSCR1.

In chromosomally normal mice, the standard two copies of the Dscr1 gene produce just enough protein to help reign in normal blood-vessel growth, but not enough to stem the angiogenesis overload triggered by a developing tumor. But in mice with an artificial version of Down syndrome (and thus a third copy of the Dscr1 gene), Ryeom found that the surplus of DSCR1 protein kept abnormal angiogenesis--and the resulting tumor proliferation--in check.

While Ryeom and her colleagues suspect that DSCR1 works in concert with a handful of other chromosome 21 genes, they confirmed that the protein plays a central role in tumor suppression. A third copy of the Dscr1 gene alone was enough to stifle cancer formation in otherwise normal mice, though not to the same degree as in the Down syndrome mice.

To confirm that the gene is relevant in human cancers, Ryeom and her colleagues created a custom line of stem cells from skin cells taken from an individual with Down syndrome. Using a relatively new technique called induced pluripotent stem (iPS) cell reprogramming, researchers can express specific genes in differentiated adult cells and revert them to an earlier developmental state, where they are capable of giving rise to many different cell types.