CLEVELAND -- Researchers at Case Western Reserve University School of Medicine have identified a "switch" that appears to allow for the development of colon cancer.
Researchers focused on segments of DNA between genes and found a set of "master switches" or gene enhancer elements that turn "on and off" key genes whose altered state is a defining signature for colon cancers.
They have coined the term Variant Enhancer Loci or "VELs," to describe these master switches.
The researchers say the VELs or switches are not mutations but changes in proteins that bind to DNA. The difference is critical because such protein changes are potentially reversible.
Researchers located the Vels or switches during a three-year study during which thousands of gene enhancer elements were mapped from normal and cancerous colon tissue samples.
In addition to finding that VELs are a "signature" of colon cancer, the team showed that genetic variants which predispose individuals to colon cancer are located within VELs. This suggests that individual differences within VELs may play significant roles in determining different individuals' susceptibility to colon cancer.
"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, Ingalls Professor of Cancer Genetics in the Division of Hematology-Oncology at the School of Medicine, member, Case Comprehensive Cancer Center, and oncologist at University Hospitals Seidman Cancer Center, whose team collaborated on the study. "The key next step will be to determine whether we can use VELs for 'personalized medicine,' to molecularly define distinct groups of colon cancers that differ in their clinical behavior, and to enable selection of specific drugs that will best treat a given colon tumor."
This research was supported by the National Cancer Institute, as well as the Case Comprehensive Cancer Center.