Researchers have developed a new fluorescent label that gives a clearer picture of how DNA architecture is disrupted in cancer cells. The findings could improve cancer diagnoses for patients and classification of future cancer risk.
Published today in Science Advances, the study found that the DNA-binding dye performed well in processed clinical tissue samples and generated high-quality images via superresolution fluorescence microscopy.
«My lab is focused on developing microscopy techniques to visualize the invisible,» said senior author Yang Liu, Ph.D., associate professor of medicine and bioengineering at the University of Pittsburgh. «We are one of the first groups to explore the capabilities of superresolution microscopy in the clinical realm. Previously, we improved its throughput and robustness for analysis of clinical cancer samples. Now, we have a DNA dye that is easy to use, which solves another big problem in bringing this technology to patient care.»
Inside the cell’s nucleus, DNA strands are wound around proteins like beads on a string. Pathologists routinely use traditional light microscopes to visualize disruption to this DNA-protein complex, or chromatin, as a marker of cancer or precancerous lesions.
«Although we know that chromatin is changed at the molecular scale during cancer development, we haven’t been able to clearly see what those changes are. This has bothered me for more than 10 years,» said Liu, who is also a member of the UPMC Hillman Cancer Center. «To improve cancer diagnosis, we need tools to visualize nuclear structure at much greater resolution.»
In 2014, the Nobel Prize-winning invention of superresolution fluorescence microscopy was a major step towards making Liu’s vision reality. A molecule of interest is labelled with a special fluorescent dye that flashes on and off like a blinking star. Unlike traditional fluorescence microscopy, which uses labels that glow constantly, this approach involves switching on only a subset of the labels at each moment. When several images are overlayed, the complete picture can be reconstructed — at a much higher resolution than previously possible.
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Materials provided by University of Pittsburgh. Note: Content may be edited for style and length.