Dr. Robertson, who also works in breast cancer and brain tumors as well as colon cancer, is finding patterns of genes that regulate healthy cell differentiation are shut off in cancers. "These are genes that may need to be active during a certain period of development but once you have committed to become a certain cell type, like a skin cell, you need to turn the gene off," he says.

"A lot of people think of cancer cells turning genes on, like oncogenes, that allow them to grow faster, evade immune surveillance, that sort of thing," Dr. Robertson says. "There are also many genes that they also want to turn off, like ones that tell a cell to differenitate. For a cell to become cancerous, those kinds of things have to happen. Cells that don't divide are not going to become cancer. They have to slip by the normal surveillance to survive and grow."

To find the differences, that means always looking at healthy tissue to identify the standard and how that happens. "We want to know how a normal cell knows where to put methylation," Dr. Shi says. "We don't understand that. If you look in the genome there are regions that are always methylated and regions that never are. How does a cell know that? To understand what happens when it doesn't, we need to know how the normal process is regulated."

To get a total picture, these researchers also are looking at how the enzymes that methylate DNA work and how modifications in histones, the proteins around which DNA is wrapped, can leave a gene susceptible to methylation.

Additionally, Dr. Shi, who as a postdoctoral fellow 10 years ago worked alongside Dr. Tim H.M. Huang at the University of Missouri in Columbia, Missouri, to develop some of the first technology to examine genome-scale DNA methylation, is working with an NIH initiative to refine the technology to support the genome-wide DNA methylation sequencing effort.

"The work of Drs. Robertson and Shi is eminently important for our understanding of cancer, easily translated to patients and central to the Cancer Center's mission to reduce cancer morbidity and mortality," Dr. Bhalla says.

mcg