NIH Researchers Identify Striking Genomic Signature Shared by 5 Types of Cancer

NIH researchers have identified a striking signature in tumor DNA that occurs in 5 different types of cancer. They also found evidence that this methylation signature may be present in many more types of cancer.

The specific signature results from a chemical modification of DNA called methylation, which can control the expression of genes like a dimmer on a light switch. Higher amounts of DNA methylation (hypermethylation), like that found by the researchers in some tumor DNA, decreases a gene’s activity. Based on this advance, the researchers hope to spur development of a blood test that can be used to diagnose a variety of cancers at early stages, when treatments can be most effective. The study appeared Feb. 5 in the Journal of Molecular Diagnostics.

“Finding a distinctive methylation-based signature is like looking for a spruce tree in a pine forest,” said Dr. Laura Elnitski, a computational biologist at NHGRI. “It’s a technical challenge to identify, but we found an elevated methylation signature around the gene known as ZNF154 that is unique to tumors.”

In 2013, her research group discovered a methylation mark (or signature) around ZNF154 in 15 tumor types in 13 different organs and deemed it a possible universal cancer biomarker. Biomarkers are biological molecules that indicate the presence of disease. Elnitski’s group identified the methylation mark using DNA taken from solid tumors. 

“No one in my group slept the night after that discovery,” Elnitski said. “We were so excited when we found this candidate biomarker. It’s the first of its kind to apply to so many types of cancer.” 

Elnitski will next begin screening blood samples from patients with bladder, breast, colon, pancreatic and prostate cancers to determine the accuracy of detection at low levels of circulating DNA. Tumor DNA in a person with cancer typically accounts for 1 to 10 percent of all DNA circulating in the bloodstream. The group noted that when 10 percent of the circulating DNA contains the tumor signature, the detection rate is quite good. Because the methylation could be detected at such low levels, it should be adequate to detect advanced cancer as well as some intermediate and early tumors, depending on the type.