For many cancers, doctors are increasingly looking to the DNA that solid tumors shed into the blood stream to help with diagnosis and monitoring. But brain cancer has been a different story thanks to the natural blockade created by the blood-brain barrier, according to a press release. Researchers at the University of Michigan Rogel Cancer Center and Michigan Medicine C.S. Mott Children’s Hospital, however, were optimistic that cerebrospinal fluid could be a valuable source for tumor DNA that could help monitor and treat pediatric cancer patients with aggressive brain tumors known as high-grade gliomas.
Not only do the mutations in these tumors change over time, causing shifts in potential avenues for treatment, the amount of tumor DNA in a patient’s spinal fluid can help doctor’s know whether changes observed on a patient’s imaging scans are true signs of a tumor’s progression or merely the body’s response to cancer treatments.
“We knew from past research that the genetic sequences of these tumors, including information about the mutations that are driving them, can be found in the spinal fluid — but collecting it isn’t currently part of the standard of care,” says Carl Koschmann, MD, a Mott pediatric oncologist and researcher with the Chad Carr Pediatric Brain Tumor Center at Michigan Medicine. “That’s something we have been hoping to change.”
A new study by Koschmann and a team of researchers from U-M suggests new, portable DNA sequencing technology could make such a “liquid biopsy” approach feasible. The team’s findings, which appear in Clinical Cancer Research, a journal of the American Association for Cancer Research, were the first to apply nanopore genetic sequencing technology toward this purpose.
The nanopore system works by measuring changes in electrical current as biological molecules pass through the tiny holes in a collection surface; different values correspond to different letters in the genetic code, thus allowing a DNA sequence to be read. Across nearly 130 samples, the researchers found the new approach worked well, and the results were confirmed using well-established sequencing methods.
Although these pediatric brain cancers are rare, the vast majority patients who are diagnosed with them live less than two years. So new, targeted approaches to treating high-grade gliomas in children and young adults is desperately needed — including for diffuse intrinsic pontine gliomas or DIPGs, highly aggressive tumors of the brain stem.
Exploiting the specific molecular mutations these tumors carry offer doctors’ best hope for attacking them. Sequencing tumor DNA found in cerebrospinal fluid would also allow doctors to monitor how a tumor’s mutations were changing over time and know whether any of the mutations might make specific treatments less likely to work.
