IMAGE: In this illustration, quantum dots are depicted as gold spheres that attract DNA strands linked to cancer risks. When the quantum dots are exposed to certain types of light, they...
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To detect this DNA methylation, the Johns Hopkins team found a way to single out the troublesome DNA strands that have a methyl group attached to them. Through a chemical process called bisulfite conversion, all segments that lack a methyl group are transformed into another nucleotide.

Then, another lab process is used to make additional copies of the remaining target DNA strands that are linked to cancer. During this process, two molecules are attached to opposite ends of each DNA strand. One of these molecules is a protein called biotin. The other is a fluorescent dye. These partner molecules are attached to help researchers detect and count the DNA strands that are associated with cancer.

To do this, these customized DNA strands are mixed with quantum dots, which are crystals of semiconductor material whose sizes are in the range of only few nanometers across. (A nanometer is one-billionth of a meter, far too small to see with the naked eye.).These dots are usually employed in electronic circuitry, but they have recently proved to be helpful in biological applications as well. Quantum dots are useful because they possess an important property: They easily transfer energy. When light shines on a quantum dot, the dot quickly passes this energy along to a nearby molecule, which can use the energy to emit a fluorescent glow. This behavior makes the cancer-related DNA strands light up and identify themselves.

In the Johns Hopkins cancer test, the quantum dots have been coated with a chemical that is attracted to biotin–one of the two molecules that were attached to the DNA strands. As a result, up to 60 of the targeted DNA strands can stick themselves to a single quantum dot, like arms extending from an octopus. Then, an ultraviolet light or a blue laser is aimed at the sample. The quantum dots grab this energy and immediately transfer it to the fluorescent dyes that were attached earlier to the targeted DNA strands. These dye molecules use the energy to light up.
These signals, also called fluorescence, can be detected by a machine called a spectrophotometer.

By analyzing these signals, the researchers can discover not only whether the sample contains the cancer-linked DNA but how much of the DNA methylation is present. Larger amounts can be associated with a higher cancer risk.

"This kind of information could allow a patient with positive methylation to undergo more frequent cancer screening tests. This method could replace the traditionally more invasive ways for obtaining patient samples with a simple blood test," said Vasudev J. Bailey, a biomedical engineering doctoral student from Bangalore, India, who was one of the two lead authors on the Genome Research paper. "It's also important because these test results could possibly help a doctor determine whether a particular cancer treatment is working. It could pave the way for personalized chemotherapy."

In addition, because different types of cancer exhibit distinctive genetic markers, the researchers say the test should be able to identify which specific cancer a patient may be at risk of developing. Markers for lung cancer, for example, are different from markers for leukemia.

The other lead author of the Genome Research paper was Hariharan Easwaran, a cancer biology research fellow in the Johns Hopkins School of Medicine. Along with Wang and Baylin, the other co-authors were Yi Zhang, a biomedical engineering doctoral student at Johns Hopkins; Elizabeth Griffiths, an oncology clinical fellow in the School of Medicine; Steven A. Belinsky, of the Lovelace Respiratory Research Institute in Albuquerque, N.M.; James G. Herman, a professor of cancer biology in the School of Medicine; and Hetty E. Carraway, an assistant professor of oncology in the School of Medicine.

Johns Hopkins Technology Transfer staff members have applied for international patent protection covering the testing technique and are in talks with a biotechnology company that has expressed interest in licensing the application.

The research was supported by grants from the National Cancer Institute, the National Science Foundation, the Hodson Foundation and the Flight Attendant Medical Research Institute