Cancer is a notoriously complex and often misunderstood disease.

Even by the broadest definition possible — abnormal cell growth — there are more than 100 different “types” of cancer, depending on where in the body that growth occurs. These categories can be further broken down to the point of exhaustion once you take factors like a tumor’s structure, how fast it grows, and whether it can migrate to other parts of the body into account. All of which is to say that discovering an one-size-fits-all cure or even an universal test for cancer will be much harder than people would like to assume.

A new study published Friday in The Journal of Molecular Diagnostics, however, may provide the first shaky steps towards the latter. The researchers, hailing from the National Institutes of Health (NIH), reported their success in finding an unique genetic marker shared by at least five different types of cancer. The trick was finding the remnants of DNA methylation, a normal process of gene editing that helps our cells smoothly function, in an area where it shouldn’t typically occur, at least to that degree (otherwise known as hypermethylation)

"Finding a distinctive methylation-based signature is like looking for a spruce tree in a pine forest," said senior author Dr. Laura Elnitski, a computational biologist in the Intramural Research Program at NIH's National Human Genome Research Institute (NHGRI) in a statement. "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."

An Universal Biomarker?

Among methylation’s many purposes is the controlled switching off and on of certain genes. By contrast, hypermethylation is believed to inadvertently shut off genes that might otherwise prevent a tumor from emerging. Although its exact role in cancer development is still being figured out, hypermethylation is known to occur in nearly all tumors, making it a prime candidate for an universal biomarker. In fact, as the researchers note, there are already tests that can detect a tumor’s methylation signature, though these are tuned to a specific type of cancer.

For this latest study, Elnitski and her colleagues took colon, lung, breast, stomach, and endometrial (the inner lining of the uterus) tumor samples and compared them to their corresponding normal counterparts, using a method known as bisulfite amplicon sequencing to trace out their respective patterns of methylation. They specifically keyed in on ZNF154 because earlier research of theirs found evidence of hypermethylation there across 15 different tumor types in 13 different organs.

Sure enough, they found it again in the newer samples. "Furthermore, this hypermethylation occurred in most tumors examined, regardless of subtype, stage of differentiation, age, or sex," they wrote. "The discrimination between all tumor sub-types and normal controls was most prominent in endometrial, colon, and lung tissues."

Because cancer cells — and normal cells — often shed some of their DNA into the bloodstream, a phenomenon plainly known as circulating tumor DNA (ctDNA), it’s possible ZNF154’s methylation signature may allow us to craft together a reliable blood test for it. In an accompanying computer model of how such a test might work, the team found that if at least 10 percent of the DNA swimming around in the blood was of the tumor’s, their detection rates were superb. And even when levels dropped to the single-digits, their accuracy remained robust. "Such sensitivity should be adequate to detect advanced cancer and some intermediate and early tumors, depending on the tumor type," they concluded.

Of course, there’s plenty of research to look ahead to, not only in making sure that ZNF154 hypermethylation in cancer cells is as universal as it appears, but even in figuring out ZNF154’s actual purpose in the human body. Still, the future is bright for Elnitski and her team. They will next work together with Dr. Christina Annunziata, head of the Translational Genomics Section at NIH's National Cancer Institute in order to test out their technique on women with ovarian cancer. The hope is that the method might help patients better monitor the recurrence of tumors following treatment.

"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.

Dr. Elnitski is also the head of the Genomic Functional Analysis Section and senior investigator in the Translational and Functional Genomics Branch at NHGRI.

Source: Margolin G, Petrykowska H, Jameel N, et al. Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus with in Silico Modeling for Blood-Based Diagnostic Development. The Journal of Molecular Diagnostics. 2016.