HMS researchers have identified a gene whose extra copy in Down syndrome inhibits the growth of solid tumors. The paradoxical discovery confirms a hunch that a gene or genes found in triplicate in people with the disease—marked by three copies of chromosome 21—may confer protection against cancer. Studies show that people with Down syndrome get far fewer tumors than those with the normal complement of two copies of the chromosome.
The lab of Sandra Ryeom, HMS instructor in surgery at Children’s Hospital Boston, identified the gene, DSCR1, and confirmed that mice with a single extra copy had significantly fewer tumors than those without. Activated in cells that form blood vessels, the gene, when expressed in threes, blocks the production of vessels that feed tumors. In collaboration with George Daley, HMS associate professor of biological chemistry and molecular pharmacology, and using a stem cell–based tumor model, the team showed that the gene similarly suppresses blood vessel formation in tumors derived from Down syndrome human cells.
Ryeom envisions that the discovery could lead to preventive therapy for patients at high risk of developing solid tumors. Her lab is investigating ways to use a fragment of the gene’s protein product as a drug candidate. The challenges ahead involve delivering this peptide into target cells where it can mimic the protective effects of the triplicate gene and determining if the peptide causes unwanted side effects. For details, see the study by first author Kwan-Hyuck Baek in the May 20 Nature.
Students may contact George Daley at george.daley@childrens.harvard.edu for more information about the stem cell work or William Aird at waird@bidmc.harvard.edu for more information on the mouse models.
Conflict Disclosure: The authors report no conflicts.
Funding Sources: The Howard Hughes Medical Institute; Harvard Stem Cell Institute; National Institutes of Health; National Heart, Lung and Blood Institute; Jerome Lejeune Foundation; Uniformed Services University of the Health Sciences; Smith Family Medical Foundation; Garrett B. Smith Foundation; and Annie’s Fun Foundation; the content of the work is the responsibility solely of the authors.
