Tumor DNA in Spinal Fluid Could Help Doctors Better Monitor Childhood Brain Cancer

Researchers have demonstrated that a new liquid biopsy approach overcomes traditional barriers to quickly and efficiently diagnose and monitor high-grade gliomas.

9:53 AM

Author | Ian Demsky

glioma device computer showing data in red blue and green lines about cancer
Illustration: Stephanie King

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.

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 a 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, M.D., 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.

"We used a modern, handheld DNA sequencing device in a way that had never been done before," says study first author Amy Bruzek, M.D., a neurosurgery resident at Michigan Medicine. "This allowed us to analyze the tumor DNA in patients' cerebrospinal fluid quickly and with equipment that's portable enough to bring into the operating room."

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.

We used a modern, handheld DNA sequencing device in a way that had never been done before.
Amy Bruzek, M.D., M.S.

The study looked for clinically actionable alternations in samples from 12 patients with high-grade gliomas using a device made by Oxford Nanopore Technologies, a spinout from the University of Oxford. The device costs about $1,000, weighs one pound and can be connected to a laptop, the researchers note, giving it advantages over leading laboratory models, which often cost tens of thousands, require dedicated space and are more complex to operate. It also requires significantly smaller amounts of spinal fluid than other sequencing methods.

Across nearly 130 samples, the researchers found the new approach worked well, and the results were confirmed using well-established sequencing methods.

"This study shows an opportunity to efficiently monitor how well clinical trial medications are working for pediatric glioma patients by collecting spinal fluid at different points in time using a procedure known as lumbar puncture or spinal tap," Bruzek says.

Currently, after an initial surgery to remove as much of a glioma as possible, doctors track changes to a tumor by looking at imaging scans.

"Unfortunately, good responses to radiation therapy can create swelling that looks very similar to a tumor that is growing," Koschmann says. "And as doctors, we have to tell patients' families the images can't be interpreted with certainty."

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.

"As caregivers, we're excited about the possibility of monitoring tumors without exposing patients to potential complications from invasive surgeries," Koschmann says. "This approach suggests we can rapidly and reliably detect key tumor-driving mutations in high-grade gliomas with very small samples — overcoming some of the barriers that were preventing the use of spinal cord fluid in diagnosing and monitoring these patients. And we're optimistic about incorporating this approach into clinical trial design for pediatric brain cancer, allowing us to track molecular response across multiple genes to better understand and predict clinical outcomes."

The research was supported by the National Institute of Neurological Disorders and Stroke (K08-NS099427–01), the U-M Chad Carr Pediatric Brain Tumor Center, Catching Up With Jack. the Evans family, the Chad Tough Foundation, Michael Miller Memorial Foundation, the Prayers from Maria Foundation, the U CAN-CER VIVE Foundation, the Morgan Behen Golf Classic and the DIPG Collaborative.

Additional authors include: Karthik Ravi, Ashwath Muruganand, Jack Wadden, Clarissa May Babila, Evan Cantor, Leo Tunkle, Kyle Wierzbicki, Stefanie Stallard, Robert P. Dickson, Ian Wolfe, Rajen Mody, Andrea Franson, Patricia L. Robertson, Karin M. Muraszko, Cormac O. Maher, Hugh J.L. Garton, and Tingtin Qin, all of U-M. And Jonathan Schwartz of the Mayo Clinic.

Paper Cited: "Electronic DNA Analysis of CSF Cell-free Tumor DNA to Quantify Multi-gene Molecular Response in Pediatric High-grade Glioma," Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-20-2066


More Articles About: Health Tech Brain Cancer Cancer Research CS Mott Children's Hospital Children's Health Cancer: Cancer Types
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of healthcare news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]

734-764-2220

Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Subscribe
Featured News & Stories cancer cell blue yellow
Health Lab
Widening inequality seen where cancer clinical trials are available
The availability of clinical trials of new treatments for cancer varies greatly by geography, and a new study shows more socially vulnerable areas have far fewer.
The Fundamentals Podcast Hero Card Final 1800 x 1350
The Fundamentals
If they don't give up, how can I give up?
Today on The Fundamentals is Dr. Maria Castro, the R.C. Schneider collegiate professor of neurosurgery, and a professor of cell and developmental biology at the University of Michigan Medical School. Her research program aims to develop immunotherapies for primary and metastatic brain cancer, studying basic immune biology mechanisms leading to clinical implementation. She has been inducted into the American Association for the Advancement of Sciences, the Latin American Academy of Sciences, and the American Institute for Medical and Biological Engineering College of Fellows. She has won numerous awards for her contributions to basic science and cancer research and is a diversity ambassador for the Cancer Biology Graduate Training Program. You can learn more about Dr. Castro here, and you can follow her @castro2355_mg, the Rogel Cancer Center @UMRogelCancer, the department of neurosurgery @umichneuro, Michigan Neurscience Institute @UM_MNI and the department of cell and developmental biology @UMCDB on X
Health Lab
Mother-son heart bond: Woman relives congenital heart journey through newborn
A mother relives congenital heart journey through newborn.
stained glass green blue purple orange pink
Health Lab
Massive study identifies new biomarkers for renal cancer subtypes, improving diagnosis and—eventually—treatment
A study led by University of Michigan Health Rogel Cancer Center researchers identifies novel biomarkers in renal cell carcinomas.
woman holding blackboard sign and poster next to her in purple
Health Lab
A mother’s tragedy leads to a new resource for grieving parents
Created by a patient and grieving parent, a peer and medically reviewed guidebook on pregnancy and infant loss offers others going through the same experience more resources during the difficult time.
10 year old boy leaning against tree and posing with his mom and sisters outside
Health Lab
Family travels over 1,000 miles for son’s heart transplant
Family travels over 1,000 miles for son's heart transplant and ongoing heart care