Visualizing the Invisible: New Fluorescent DNA Label Reveals Nanoscopic Cancer Features
“Early-stage lesions can have very different clinical outcomes,” said Liu. “Some people develop cancer very quickly, and others stay at the precursor stage for a long time. Stratifying cancer risk is a major challenge in cancer prevention.”
To see if chromatin structure could hold clues about future cancer risk, Liu and her team evaluated patients with Lynch syndrome, a heritable condition that increases the risk of several cancer types, including colon cancer. They looked at non-cancerous colorectal tissue from healthy people without Lynch syndrome and Lynch patients with or without a personal history of cancer.
The differences were striking. In Lynch patients who previously had colon cancer, chromatin was much less condensed than in healthy samples, suggesting that chromatin disruption could be an early sign of cancer development — even in tissue that looks completely normal to pathologists.
For Lynch patients without a personal history of cancer, some will go on to develop cancer, while others will not. “We see a much larger spread in this group, which is very interesting,” said Liu. “Some patients resemble healthy controls, and some are closer to Lynch patients who previously had cancer. We think that patients with more open chromatin are those who are more likely to develop cancer. We need to follow these patients over time to measure outcomes, but we’re pretty excited that chromatin disruption in normal cells could potentially predict cancer risk.”
In future work, Liu and her team are interested in examining chromatin structure in endometrial tissue from Lynch patients, who also have elevated risk of endometrial cancer. The researchers also received funding recently to look at sputum samples from smokers for early detection of lung cancer.
Other authors who contributed to this study were Jianquan Xu, Ph.D., Xuejiao Sun, M.S., Hongqiang Ma, Ph.D., Rhonda M. Brand, Ph.D., Douglas Hartman, M.D., and Randall E. Brand, M.D., all of Pitt; and Mingfeng Bai, Ph.D., and Kwangho Kim, Ph.D., both of Vanderbilt University.
This work was funded by the National Institutes of Health (R01CA254112, R33CA225494 and R01CA232593).
PHOTO INFO: (click images for high-res versions)
CAPTION: Dr. Yang Liu, associate professor of medicine and bioengineering at the University of Pittsburgh and member of the UPMC Hillman Cancer Center
CAPTION: A new fluorescent label called Hoechst-Cy5 gives a clearer picture of how DNA architecture is disrupted in cancer cells.
CREDIT: Xu, J. et al. Science Advances 8, eabm8293 (2022)
Manager, Science Writing
Director, Science and Research