CLEVELAND—A team of researchers at Case Western Reserve University School of Medicine have identified a new mechanism by which colon cancer develops. By focusing on segments of DNA located between genes, or so-called “junk DNA," the team has discovered a set of master switches, i.e., gene enhancer elements, that turn “on and off" key genes whose altered expression is defining for colon cancers. They have coined the term Variant Enhancer Loci or “VELs," to describe these master switches.
Importantly, VELs are not mutations in the actual DNA sequence, but rather are changes in proteins that bind to DNA, a type of alteration known as “epigenetic" or “epimutations." This is a critical finding because such epimutations are potentially reversible.
Over the course of three years, the team mapped the locations of hundreds of thousands of gene enhancer elements in DNA from normal and cancerous colon tissues, 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," said Peter Scacheri, PhD, senior author of the study and assistant professor, Genetics and Genome Sciences, School of Medicine, and member, Case Comprehensive Cancer Center at Case Western Reserve University. “The set of common VELs govern a distinct set of genes that go awry in colon cancer."