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You probably know that DNA, the molecule inside every cell that contains a blueprint for the development and function of an organism, comprises two long chains that form a double helix. The two strands are composed of a code of four molecular letters, A, T, C, and G. The letters on each strand are paired with letters on the other strand in a specific way: A pairs with T, and C with G. When a pair of these letters change—for example, an A:T pair changing to a C:G pair—it’s called a mutation, an alteration that can lead to cancer or a variety of genetic diseases.

However, mutations usually begin with a change in only one of the two DNA strands, such as when the G in a C:G pair changes to a T, creating a mismatched C:T pair. Fortunately, such mismatches occur only rarely. “And when they do, our cells fix them most of the time,” explains , a member of ��ɫtv Langone Health’s . But if the mismatch in one strand is not repaired, it can cause a corresponding change to the other strand, leading to a permanent mutation.

“Mutations are responsible for an immense burden of disease,” Dr. Evrony says. They elevate a person’s risk for many types of cancer, and when combined with environmental risk factors, can lead to many other health conditions.

What if those single strand molecular changes in the DNA code could be detected before they become mutations? A pioneering technique developed by Dr. Evrony and his research team, along with international collaborators, is designed to do just that.

Hairpin Duplex Enhanced Fidelity Sequencing, or HiDEF-seq, can read the billions of A, T, C, and G bases comprising each DNA strand with unparalleled accuracy. While other scientists have developed methods to “see” changes that are present in both DNA strands, Dr. Evrony’s project went a step further. The study, , demonstrates an approach that for the first time accurately detects DNA changes in only one strand, when they can still be repaired. The research may advance our understanding of the basic causes of mutations in both healthy cells and cancerous ones.

For their research, Dr. Evrony and colleagues examined DNA from people with syndromes that predispose them to cancer. They found that subjects with polymerase proofreading–associated polyposis, a hereditary condition linked to colorectal cancer, or with congenital mismatch repair deficiency, a genetic condition that increases the risk of childhood cancer, had substantially more DNA mismatches even in their healthy cells. The technique can also detect a common type of DNA change called cytosine deamination—when a C base on one of the two DNA strands is damaged, potentially leading to mutations.

Eventually, the hopes to identify DNA damage that occurs as a result of environmental exposures and chemotherapy. Such advances could one day lead to methods for reducing the rate at which our DNA mutates and might even aid in improving treatments for cancer.

“We’re laying the groundwork to measure to what degree people have differences in their DNA repair, and predict their risk for cancer,” Dr. Evrony says. “Those are potential applications on the five-year horizon. It’s ambitious but not impossible.”