Down Syndrome Related Genes May Protect Against Solid Tumors

Researchers from Stanley Manne Children’s Research Institute have discovered that a set of genes in individuals with Down Syndrome may not only lead to clinical abnormalities—such as muscle development issues or heart problems—but may also protect them from developing solid tumors. Their results were published today in Scientific Reports.

"Our promising preliminary data carries strong potential for ultimately developing gene-targeted therapies to inhibit solid tumor growth in the general population," says co-lead author Yekaterina Galat. "Our findings may also provide gene targets for therapies aimed at alleviating the clinical abnormalities in people with Down syndrome."

The team used skin samples from patients with Down Syndrome and developed induced pluripotent stem cells that were later differentiated into endothelial and mesodermal cells. It was during the differentiation process, that the researchers discovered that down-regulated genes that are involved in abnormal muscle development and heart problems—two common complications of Down Syndrome—may be involved in other pathways as well. 

They studied the genes and their role in biochemical pathways that are relevant to tumor development and found that decreased expression of such genes intervenes with the processes required for solid tumor formation and growth. Specifically, they observed that the genes impede cell movement, cause slower proliferation and a reduced inflammatory response—curating a hostile microenvironment for tumors. Genome-wide analyses of over 11,000 patients confirmed these findings. 

"When we performed genomic analyses comparing mesodermal and endothelial cell lines, we were surprised to find that trisomy 21 impacted gene expression across the entire genome. Furthermore, the decreased expression of the genes we studied was consistent, and the large extent of their down-regulation was notable as well," says co-lead author Mariana Perepitchka. "This significant down-regulation potentially creates conditions that are opposite of what solid tumors would need to take hold. So in a way, Down syndrome provides us with a non-traditional lens to study cancer development."