Researchers Identify Tumor Signature That Serves as a Biomarker of at Least 5 Types of Cancer

A methylation signature was identified in 5 types of cancer, and it likely occurs in more. These findings may aid in developing a blood test to diagnose cancer at early stages, when it is most treatable. The study was published in The Journal of Molecular Diagnostics.1

Methylation of DNA is a chemical modification, and hypermethylation decreases a gene's activity.

"Finding a distinctive methylation-based signature is like looking for a spruce tree in a pine forest," said Laura Elnitski, PhD, a computational biologist in the Intramural Research Program at National Institutes of Health National Human Genome Research Institute (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." Elnitski is head of the Genomic Functional Analysis Section and senior investigator in the Translational and Functional Genomics Branch at NHGRI.

In 2013, her research group discovered a methylation mark (signature) around ZNF154 in 15 tumor types in 13 different organs and deemed it a possible universal cancer biomarker. 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."

This new study examined colon, lung, breast, stomach, and endometrial cancers, and the same methylation mark around ZNF154 was found in all the tumor types and subtypes. The researchers compared methylation in people with and without cancer.

The researchers developed a series of steps that uncovered telltale methylation marks in colon, lung, breast, stomach, and endometrial cancers. They showed that all the tumor types and subtypes consistently produced the same methylation mark around ZNF154.

Next, the research team plans to screen blood samples for circulating tumor DNA, which typically is 1% to 10% of the DNA in the bloodstream of a person with cancer. One focus of these efforts will be ovarian cancer, which is difficult to detect in its early stages.

"We have laid the groundwork for developing a diagnostic test, which offers the hope of catching cancer earlier and dramatically improving the survival rate of people with many types of cancer," Elnitski said.


1. Margolin G, Petrykowska HM, Jameel N, Bell DW, Young AC, Elnitski L. Robust detection of DNA hypermethylation of ZNF154 as a pan-cancer locus with in silico modeling for blood-based diagnostic development. J Mol Diagn. 2016;18(2):283-298.

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