Solid tumors are very rare in people with Down syndrome. Why? The answer almost certainly lies among the 231 extra genes they inherit with their extra copy of chromosome 21.
Narrowing the search for the anti-cancer gene is another observation: People with Down syndrome rarely get diseases linked to the overgrowth of blood vessels.
Might the anti-cancer effect of Down syndrome be linked to something that blocks the growth of new blood vessels? To find out, Sandra Ryeom, PhD, and colleagues at Children's Hospital Boston designed a clever series of experiments.
One of the genes on chromosome 21 encodes a protein that blocks a factor needed for blood vessel growth. They found that this protein, DSCR1, is overproduced in people with Down syndrome. It's also overproduced in about the same amounts in a mouse model of Down syndrome.
Might the extra protein really affect blood vessel growth? When Ryeom and colleagues looked at tumors grown from Down syndrome stem cells, they saw that these cancer cells had fewer blood vessels than cancers grown from normal stem cells.
Further experiments confirmed that DSCR1 inhibited angiogenesis, or blood vessel growth.
Given that people with Down syndrome have 231 extra genes, it's improbable that DSCR1 is the only one with anti-cancer effects. And Ryeom and colleagues found evidence that another chromosome 21 gene, Dyrk1A, contributes to the anti-angiogenesis effect.
"I think there may be four or five genes on chromosome 21 that are necessary for angiogenesis suppression," Ryeom says in a news release.
"It is, perhaps, inspiring that the Down syndrome population provides us with new insight into mechanisms that regulate cancer growth and, by so doing, identifies potential targets for tumor prevention and therapy," Ryeom and colleagues conclude.
The findings appear in the early online edition of the journal Nature.