Researchers from the Case Western Reserve University School of Medicine have discovered a new mechanism by which colon cancer develops. Whilst concentrating on ‘junk DNA’ i.e. DNA segments located between genes, the team found a set of master switches (gene enhancer elements) that turn key genes on and off. An alteration in the expression of these genes leads to colon cancers. To describe these master switches, the team has named them Variant Enhancer Loci or ‘VELs’.
The team points out that VELs are not mutations in the actual DNA sequence, but changes in proteins that bind to DNA. This form of alteration is also known as ‘epigenetic’ or ‘epimutations’. The finding is significant, given that such epimutations can potentially be reversed.
Over a 3-year period, the team systematically recorded the locations of hundreds of thousands of gene enhancer elements in DNA from normal and cancerous colon tissues and identified key target VELs that were different between the two tissue types.
Senior researcher, Peter Scacheri, PhD, assistant professor of Genetics and Genome Sciences at the School of Medicine and member of Case Comprehensive Cancer Center at Case Western Reserve University states:
“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. The set of common VELs govern a distinct set of genes that go awry in colon cancer.”
Sanford Markowitz, MD, PhD, Ingalls Professor of Cancer Genetics in the Division of Hematology-Oncology at the School of Medicine and member of Case Comprehensive Cancer Center, who is also an oncologist at the University Hospitals Seidman Cancer Center, and whose team collaborated on the study, adds:
“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. 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.”
Aside from discovering that VELs are a ‘signature’ of colon cancer, the team also demonstrated that VELs contain genetic variants that govern which people will be likely to suffer from colon cancer. This indicates that individual differences within VELs may play an important part in establishing different people’s susceptibility to colon cancer.
Lead author, Batool Akhtar-Zaidi, PhD candidate in Dr. Scacheri’s lab explains:
“Epigenetics has transformed the way we think about genomes. The genetic code isn’t just a series of As, Ts, Gs, and Cs strung together. Epigenetic ‘marks’ on DNA tell genes when, where, and how much to turn on or off to keep cells healthy. When this epigenetic machinery is disrupted, as we see with VEL events, this can tip the balance to cancer.”
Written By Petra Rattue