Summer
2012

Discovery

Researchers Find Master Switches for Colon Cancer

Researchers Find Master Switches for Colon Cancer


Case Western Reserve University School of Medicine researchers have identified a set of master switches that control key genes involved in colon cancer.

A team of researchers discovered a set of gene enhancer elements buried in so-called “junk” DNA—the segments of DNA located between genes. The enhancers, which the researchers named Variant Enhancer Loci, or VELs, serve as switches to activate or deactivate key genes linked to colon cancer.

And unlike mutations in the actual DNA sequence, VELs could be reversible, making them a potential target for treatment.

The team mapped the locations of thousands of gene enhancer elements in DNA from both normal and cancerous colon tissue, pinpointing key target VELs that differed between the two types.

“What is particularly interesting is that VELs define a ‘molecular signature’ of colon cancer. Meaning, they are consistently found across multiple independent colon tumor samples, despite the fact that the tumors arose in different individuals and are at different stages of the disease,” says Peter Scacheri, PhD, senior author of the paper, which was published in the May issue of Science, and assistant professor of genetics and genome sciences.

“The VELs signature is notable because it cuts through the complexity of the many genes that are changed in colon cancer to identify genes that are direct targets of alterations on chromosomes,” says Sanford Markowitz, MD, PhD, the Dr. Sanford Markowitz/Frances Wragg Ingalls Professor of Cancer Genetics at the School of Medicine and a medical oncologist at University Hospitals Seidman Cancer Center, whose team collaborated on the study1.

The next step will be to determine if VELs can be used for personalized medicine by defining distinct molecular groups of colon cancers and enabling the selection of specific drugs to treat them.

1 Research funded by NIH grant Nos.R0-HD056369, R01-CA160356, R01-CA1555004, R01-LM009012, R01-LM010098 1P50-CA150964, UO1-CA152756 and 5T32GM008056-29.