The Center for Cancer Epigenetics

THE CHALLENGE Epigenetics is the key to reading the WHY genetic code in different ways and While the Human Genome Project mapped our genes, NOW? ultimately altering the code to coax the resulting “blueprint” fails to account for malignant disease cells, which begin as normal cells, to return to their proper behavior. This area of cells whose genetic codings actually appear normal. research holds such great promise that the National Scientists at The University of Texas MD Anderson Institutes of Health has designated it as a major Cancer Center believe the answer to this quandary lies “Roadmap” initiative to speed its development. The in the study of epigenetics—changes in gene expression study of epigenetics has the potential to explain the that occur without altering basic DNA structure. mechanisms that lead not only to cancer, but to aging, These epigenetic changes include DNA methylation, a heart disease, mental health and other conditions. chemical alteration that prevents the reading of protein- making instructions contained in genes, and histone turn critical genes back on—including those known to deacetylation, which suppress tumors. These new therapies will be designed results in the same to manipulate wayward genes to return to their original outcome by keeping activities rather than to kill tumor cells, a treatment DNA strands wound approach with reduced toxicity and fewer side effects. tightly around spool- like histone proteins. EPIGENETICS IN ACTION This shutdown of the protein-making Research in Dr. Issa’s lab has shown that environmental process (essential to factors—lifestyle, diet and geographic location, for normal functioning example—can affect the DNA methylation status of as protein molecules genes in normal tissues and potentially result in pre- Identical twins have identical activate other cancerous or cancerous conditions. His work helped lead genes. However, differences in genes and carry to Food and Drug Administration approval of decitabine their epigenomes, which control out virtually every (which affects DNA methylation) as the standard of how genes behave, can explain other cell task) leads disparities in their health. care in myelodysplastics syndrome, a precursor of acute to malfunctioning myelogenous leukemia. genes and mechanisms that can impact disease development and Dr. Dent and her team are leading research on the role progression. Thus epigenetic changes, which can be of chromatin-remodeling enzymes in gene expression inherited or acquired, are now thought to be just as and how they contribute to cell growth and development. important in cancer formation as genetic mutations. Chromatin is a mix of mostly DNA and specialized proteins called histones that help control gene behavior. THE OPPORTUNITY THE IMPACT OF GIVING But unlike genetic mutations, epigenetic changes can be reversed. At the Center for Cancer Epigenetics Philanthropic support is essential to advancing research (CCE)—one of seven centers of excellence in at the CCE. The center seeks $5 million to provide MD Anderson’s Institute of Basic Science—more than seed funding for novel research projects (to collect 30 scientists in a dozen-plus disciplines are working the preliminary data needed to effectively compete for to unveil links between cancer and specific epigenetic federal funding); aid new faculty recruitment; support actions which switch gene functions on and off. Led by educational programs to train the next generation of Co-directors Sharon R. Dent, Ph.D., and Jean-Pierre epigenetics researchers; fund data and information Issa, M.D., CCE efforts to define the full spectrum exchange; and sustain the Solexa Deep-Sequencing of epigenetic markers in normal and tumor cells and Facility, a state-of-the-art technology center used to to determine the mechanisms that drive epigenetic map the locations of individual epigenetic markers changes will ultimately lead to new therapies that can across entire genomes.

The University of Texas MD Anderson Cancer Center June 2010