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Getting to the root of cancer by examining protein binding

In a new study, a team of researchers has examined the relationship between protein binding to DNA and the development of cancer.

As a dermatologist and a genetics researcher, Howard Chang, MD, PhD, sees cancer through more than one lens. Not only does he examine cancerous cells through a microscope, but he also witnesses the impact of cancer on patients and loved ones firsthand.

Chang is using his specialized experience to get to the bottom of the disease by looking at how changes in protein binding can affect the development of cancer.

DNA is tightly coiled, with only small stretches exposed to binding proteins that regulate how genes are expressed. Using a technique that Chang likened to "spray-painting your DNA", where only the exposed DNA is painted, the researchers were able to identify unusual binding sites where proteins could attach, potentially triggering biological changes or even cancer.

The study appears in Science.

Using the "spray-painting" technique called assay for transposase-accessible chromatin using sequencing, or ATAC-seq, they discovered that different cancers have specific protein-binding patterns.

This finding helps deepen our understanding of the onset of cancer. As Chang explains in the Stanford Medicine news release:

These switches that determine gene activity were our missing component... We can now find how these switches are changing cancer, including mutations that make the switch get stuck on the on position.

By identifying where the cancer begins, Chang hopes that physicians can stop the mutation before it has the time to grow and cause significant damage to patients.

Ryan Corces, PhD, one of the study's lead authors, believes this finding will lead to a change in the future of cancer research.

From the article:

Although the team’s findings have yet to be applied in a clinical setting, the researchers believe their work will be useful in the development of better cancer prognoses, more information on patient susceptibility to cancer and new treatments that are more localized and effective.

Beyond its potential clinical impact, Corces said he believes the research provides valuable knowledge about cancer gene regulation.

Photo by Darryl Leja, NHGRI

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