A New Type of Liquid Biopsy

Biopsy. It can bring to mind painful cutting, punching and poking. Thankfully, these important and potentially life-saving procedures have moved into the new millennium along with the rest of us.

Liquid biopsies have become a hot area of development in cancer diagnostics. These tests arise from the simple fact that tumors shed DNA and cells. It’s possible to detect these tumor leftovers in bodily fluids such as blood, urine, or saliva. So liquid biopsies present a much more attractive alternative than traditional and often repeated tissue biopsies to screen for cancer and monitor treatments. However, one major drawback exists. Current versions use pricey, lab-based technologies such as DNA sequencing to detect cancer markers.

Fortunately, there may soon be a new liquid biopsy in town. The new tests detect epigenetic markers, rather than genetic mutations. They could prove to be less expensive, faster, and easier to administer.

Term of Week: Epigenetics

Epigenetic modifications are changes to DNA that don’t alter the actual gene sequence themselves, like mutations. Instead, they are chemical modifications to the DNA. These alterations typically affect gene expression, that is, how often a gene gets read by the cell.

One of the most common types of epigenetic modifications is methylation—the addition of a methyl (CH3) group to cytosine (C) nucleotides.

The end result: methylation reduces or even blocks gene expression. Areas of the genome that have methyl groups attached to them are referred to as methylated. DNA methylation is a normal part of cellular development. However, variations in the “normal” methylation pattern are associated with disease.

The Cancer Methylscape

Last fall, researchers at the University of Queensland (Brisbane, Australia) published work describing a “methylscape” (methylation pattern) that is common to most cancers. They found that in many cancer cell genomes, regulatory regions—which help control gene expression—are methylated significantly more than normal. In contrast, other parts of the genome display much less methylation than normal.

Such differences in methylation patterns change the structure of DNA. This, in turn, determines what else interacts with the DNA. In their study, the University of Queensland team found that DNA that exhibits a cancer methylscape binds and sticks to gold nanoparticles much better than DNA from healthy cells. (Article continues below)

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A Golden Test

Any identifiable difference between healthy and unhealthy tissue can provide a basis for a diagnostic test. Find the disease-associated variance, diagnose the illness. The University of Queensland researchers have used the gold nanoparticle affinity difference as the basis of a potential new way to identify the presence of cancer from cancer cell DNA that may be present in a blood or other fluid sample—i.e., a liquid biopsy. It’s officially called the “salt-induced gold nanoparticle aggregation system,” or gold nanoparticle test for short. It relies on the fact that adding salt to a gold nanoparticle solution causes the nanoparticles to aggregate, resulting in a color change from reddish to blue. If DNA is attached to the nanoparticles, however, no aggregation occurs, and thus no color change. This test is used to differentiate between cancer cell DNA and healthy DNA as follows:

  • DNA is added to the nanoparticle solution.
  • Cancer methylscape DNA sticks to gold nanoparticles, preventing aggregation; DNA from healthy cells doesn’t.
  • In the next step, salt is added. If the nanoparticles fail to aggregate (cancer DNA), the solution’s color remains the same. If they do (healthy DNA), the solution’s color changes.

Using this technique, the University of Queensland team identified malignant cell-derived DNA with a stunning 90 percent accuracy. They examined more than two hundred tissue and blood samples. The types of cancers tested included breast, prostate, bowel and lymphoma. The methylation pattern that underlies the test is consistent across most types of cancer, so it’s likely that the test could detect many other cancers as well.

Universal, Inexpensive, Fast, Portable!

There is potentially much to love about the new gold nanoparticle test. Its universality gives it a huge advantage over other biopsies. It could make an ideal screening for many sorts of cancer and for monitoring treatment.

Other advantages include the test’s 10-minute turnaround time and lower cost. Despite its reliance on gold, researchers anticipate a significant cost savings. That’s because the test uses a miniscule amount of the shiny stuff, especially in comparison with the cost of current liquid biopsies that rely on DNA sequencing. Finally, the new test is much more portable than large sequencing machines, meaning that technicians may be able to administer it right in a doctor’s office.

The researchers are working with UniQuest, the University of Queensland’s commercial partner, to identify a commercial partner and move into clinical testing. Only time will tell, but this innovative new test could dramatically change the cancer diagnostics landscape.

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