Researchers have developed a new fluorescent label that visualizes how DNA architecture is disrupted in cancer cells. The findings may improve cancer diagnosis.
The authors of the new work used a DNA-binding dye that creates high-quality images using super-resolution fluorescence microscopy.
My lab is focused on developing microscopy techniques to visualize things that cannot be seen with the normal eye. Our group is one of the first to explore the possibilities of super-resolution microscopy for the clinical field. We have previously improved throughput and reliability to analyze clinical cancer samples. We now have a DNA dye that is easy to use. It solves another big problem when introducing this technology into patient care.
Yang Liu, Ph.D., associate professor of medicine and bioengineering at the University of Pittsburgh
Inside the nucleus of a cell, there are strands of DNA that are wrapped around proteins. It’s like beads on a string. Doctors typically use traditional light microscopes to look for damage in the DNA-protein complex, or chromatin, a marker of cancer or precancerous lesions.
The team has developed a new label called Hoechst-Cy5. The authors combined a Cy5 DNA-binding molecule and a fluorescent dye called Hoechst.
The new marker renders better than other dyes. During the experiment, the researchers compared colorectal tissue with precancerous and cancerous lesions. In the latter, chromatin, the nucleoprotein that forms the basis of chromosomes, was densely packed, especially along the edges of the nucleus. The condensed DNA glowed brightly because a higher marker density creates a stronger signal. If the chromatin is loosely packed, then the light is dimmer.
To find out if chromatin structure can provide insight into cancer risk, Liu and her team studied patients with Lynch syndrome, an inherited condition that increases the risk of developing several types of cancer, including colon cancer. They studied non-cancerous colorectal tissue of healthy people and patients with Lynch syndrome.
The differences were amazing. In patients with Lynch syndrome who had previously had colon cancer, chromatin was much less condensed than in healthy samples. This suggests that chromatin disruption could be an early sign of cancer — even in tissue that looks completely normal.