University of Vermont

Vermont Cancer Center Awarded $2.1 Million Grant to Establish Epigenetic Tumor Signatures

Gary Stein, Ph.D.
Professor and Chair of Biochemistry Gary Stein, Ph.D. (Photo by Raj Chawla, UVM Medical Photography)

The field of epigenetics – the study of heritable, but reversible changes in gene function that do not involve changes in DNA sequence – has exploded over the past five years and is helping scientists worldwide gain a better understanding of how cancer develops and how this process can be modified. A team of Vermont Cancer Center researchers, led by VCC Co-director and University of Vermont Chair of Biochemistry Gary Stein, Ph.D., and Professors of Biochemistry Jane Lian, Ph.D., and Janet Stein, Ph.D., recently received a $2.1 million grant from Pfizer Pharmaceuticals to establish epigenetic signatures for risk assessment of drug-related induction of cancer and tumor progression.

“Epigenetic control provides an important dimension for monitoring the fidelity of biological regulation that accompanies the initial stages of cancer,” say Gary Stein and Jane Lian. “Both the onset and progression of cancer are associated with opposing genetic (DNA-encoded) and epigenetic (non-DNA-encoded) mechanisms that influence the transmission and retention of regulatory information during cell division. In this manner, cancer cells develop a ‘memory’ that sustains their disease state.”

Cancer tumors are composites of cells at different stages of aggressiveness and therefore, require the establishment of a detailed catalogue of the structure of cancer-related genes in order to profile a complete picture of the abnormal phenotype of cancer cells. This new project utilizes the unique state-of-the-art genomic analysis capabilities of the VCC’s Advanced Genome Technologies Core to investigate cancer treatment-related alterations in epigenetic control. These analyses will provide highly sensitive indicators of the specific and/or non-specific effects from therapy with established pharmaceuticals and drugs being developed. By using this innovative strategy, the research team hopes to establish that epigenetic changes will generate a composite signature for screening various cellular functions that have gone awry at the onset of transformation from normal to cancer cells and during further progression of the disease.

“The ‘cutting-edge’ capabilities of the Vermont Cancer Center in advanced DNA sequencing provides a window of opportunity for establishing options for targeted treatment of tumors that are maximally effective and with minimal complications,” says Gary Stein.

Stein, Lian and their research team aim to develop epigenetic profiles that will be highly informative for evaluating the specificity and activity for the next generation of options to treat tumors that do not respond well to conventional approaches.

(Drs. Gary Stein, Jane Lian, Janet Stein and colleagues contributed to this article.)