NIH researchers find genomic signature common in 5 types of cancer

NIH's Laura Elnitski

Scientists hailing from the National Institutes of Health have uncovered genomic signatures that are shared across a number of different cancers. This discovery could serve as a useful biomarker to flag cancer at an earlier stage, paving the way to earlier treatment that may help improve survival rates.

Building on earlier research, the investigators have zeroed in on DNA methylation, which changes how the cell expresses certain genes, and can also be used by researchers and doctors to distinguish a cancerous cell from a noncancerous cell.

NIH researcher Laura Elnitski and her team published their updated work in The Journal of Molecular Diagnostics earlier this month.

In 2013 they found that a particular region of DNA has a predictable status of DNA methylation which is common in 15 tumor types and 13 different organs. The DNA methylation was found around the gene ZNF154 and they quickly earmarked it as a potential biomarker.

"No one in my group slept the night after that discovery," Dr. 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."

In the current study they further explored this genomic signature around ZNF154 and show it is consistent across colon, lung, breast, stomach and endometrial cancers.

"Finding the methylation signature was an incredibly arduous and valuable process," said Dan Kastner of the NIH's National Human Genome Research Institute (NHGRI). "These findings could be an important step in developing a test to identify early cancers through a blood test."

By using a molecular biology tool to amplify genomic DNA and a computer program to process the sequenced DNA, they could reproducibly predict whether a sample was from a tumor or not even when the amount of methylated molecules were reduced by 99%. Since tumor cells leak their DNA into the blood they also developed a sensitive approach to search for these signatures in the blood.

The team's next step will be to screen blood samples taken from patients with various tumors which they will run through their diagnostic algorithms. They also plan to join forces with the Translational Genomics Section at NIH's National Cancer Institute to target ovarian cancer in women and to apply their new research.

The link between DNA methylation and cancer is not fully understood. How the signature found around the ZNF154 gene effects the function of that gene is also unclear, as well as the basic function of the gene in normal cell behavior. But the potential for developing a much more sensitive test for cancer has excited the scientists.

"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," Dr. Elnitski said.

- here's the release
- here's the journal abstract