Detection of an epigenetic signature found in five different common tumor types—colon, lung, breast, stomach, and endometrial cancers—may be useful in diagnosing early-stage tumors using a blood test. Results describing the genetic signature are published in The Journal of Molecular Diagnostics.
Laura Elnitski, PhD, a computational biologist in the Division of Intramural Research at the National Institute of Health’s National Human Genome Research Institute (NHGRI), and her colleagues previously identified hypermethylation at a genomic locus, the ZNF154 CpG island, found in 15 different solid epithelial tumor types from 13 different organs. In contrast, normal, noncancerous tissue did not have hypermethylation at this locus.
A methyl moiety can be added to DNA by a process called methylation. The degree of methylation, in other words, the number of methyl groups and their location within a promoter or gene, can dictate the level of expression of a gene. Higher amounts of DNA methylation, called hypermethylation, typically lead to a decrease in gene expression and hypomethylation to an increase in gene expression.
Previous studies have shown that tumor cells, which have different gene expression profiles compared to noncancerous cells, have sites of hypermethylation that are not found in the counterpart, healthy tissue.
In the current study, Dr. Elnitski and her colleagues compared different sequencing analyses methods that can detect DNA methylation on 184 tumor samples from five tumor types and compared to 34 samples of normal tissue.
To verify the link between the potential biomarker and cancer, the researchers used computer modeling to predict the threshold of detecting circulating tumor DNA by using parameters such as the proportion of circulating tumor DNA found in the blood. They found that even if the DNA methylation marker is rare among circulating tumor cells, the test could still detect the methylated molecules.
Both simulation models and sample analysis suggests the utility of hypermethylation at the ZNF154 CpG island as a potential cancer biomarker.
The biological function of hypermethylation at the ZNF154 CpG island in cancer and whether the site is involved in promoting tumor growth or progression is not yet clear. The gene function of the locus is also not known.
“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 in a NIH news release.
Based on these results, the researchers would next like to develop a blood test based on this biomarker to potentially diagnose several different early-stage tumors.
“Our findings suggest that hypermethylation of the ZNF154 CpG island is a relevant biomarker for identifying solid tumor DNA and may have utility as a generalizable biomarker for circulating tumor DNA,” concluded the study authors.
Next, Dr. Elnitski and colleagues plan to screen patients with bladder, breast, colon, pancreatic, and prostate cancers to assess whether the methylation marker can be detected in circulating tumor DNA.