Critical to the function of the cell is the ability to change the expression of a number of genes—known as gene expression programs—which enable a number of important events like development and cellular differentiation. However, improper changes in gene expression programs can also lead to cancer. In a study published in Science, OCI Scientist Dr. Mathieu Lupien and a group of researchers from Case Western Reserve University developed a profile of the non-genetic, known as epigenetic, changes in the elements that regulate gene expression and drive the development of colorectal cancer (CRC).
They examined the epigenetic changes that control the activity of gene enhancer elements—sites in the genome that can increase the activity of distant genes—across the entire genome of cells from early, late and metastatic stage CRC tumours. The group identified thousands of sites in the genome, termed variant enhancer loci (VEL), where epigenetic control of gene enhancer elements was either increased or decreased in cancer and represent sites of control over gene expression. Using this information, they identified the VELs that directly related, and predicted, changes in gene expression patterns in CRC, including genes known to contribute to CRC development. Furthermore, the VELs were found to controls areas of the genome associated with genetic predisposition to CRC, which provides an alternative method to disrupt specific gene enhancer elements in cancer.
“From these conclusions, we propose that consistent changes in the control of enhancer elements that drive gene expression promote CRC development,” says Dr. Lupien. “Because of their consistent and predictive nature, VELs are a great resource to define the specific nature of the tumour and treat it accordingly—the basis of personalized cancer medicine.”
Epigenomic enhancer profiling defines a signature of colon cancer. Akhtar-Zaidi B, Cowper-Sal Lari R, Corradin O, Saiakhova A, Bartels CF, Balasubramanian D, Myeroff L, Lutterbaugh J, Jarrar A, Kalady MF, Willis J, Moore JH, Tesar PJ, Laframboise T, Markowitz S, Lupien M, Scacheri PC. Science. 2012 April 12. [Pubmed abstract]
This work was supported by the National Institutes of Health.