Novel Method May Improve Cancer Detection

A novel method that threads DNA strands through a nanopore can detect, count, and map methylations with unprecedented resolution.

The findings, published in 2D Materials and Applications, may be used in the future to detect cancer early.

“One or a few methylations is not a big deal, but if there are many of them and they are packed close together, then it’s bad,” said lead investigator Jean-Pierre Leburton. “DNA methylation is actually a starting process for cancer. So, we want to detect how many of them there are and how close together they are. That can tell us at which stage the cancer is.”

Although there have been other attempts to enlist nanopores to detect methylation, the resolution has been limited.

Prior methods involved punching a tiny hole in a flat sheet of material that was only 1 atom or molecule thick. The pore is then submerged in a salt solution and an electrical current is applied to help push the DNA through the pore.

Any dips in the current signal to investigators that a methyl group is passing through. But when 2 or 3 are close together, the pore interprets it as one signal, according to the authors.

In the current study, investigators slightly altered the approach and instead applied a current directly to the conductive sheet surrounding the pore. Next, they used advanced computer simulations to test applying the current to different flat materials as methylated DNA was threaded through.

“Our simulations indicate that measuring the current through the membrane instead of just the solution around it is much more precise,” Leburton said. “If you have 2 methylations close together, even only 10 base pairs away, you continue to see 2 dips and no overlapping. We also can map where they are on the strand, so we can see how many there are and where they are.”

Currently, investigators are working in collaboration to improve the DNA threading, with a goal of cutting down on noise in the electrical signal and to conduct experiments to confirm the simulations.