New Genetic Biomarker Flags Aggressive Brain Tumors

Clinicians typically classify meningiomas — the most common type of brain tumor — into three grades, ranging from slow-growing to aggressive.

But a new multi-institutional study suggests that appearances may be deceiving. If a tumor shows activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low-grade under the microscope.

The findings, published Sept. 1 in Lancet Oncology, could significantly change how doctors diagnose and treat meningiomas.

"High TERT expression is strongly linked to faster disease progression," says Gelareh Zadeh, M.D., Ph.D., a neurosurgeon at Mayo Clinic and senior author of the study. "This makes it a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease."

An Early Warning Sign

Meningiomas — tumors of the meninges, the protective tissue that surrounds the brain and spinal cord — are generally considered benign. But a small subset of these tumors has a mutation in the TERT gene, which is linked to faster growth and a shorter time before the tumor returns after treatment.

TERT is the active part of telomerase, an enzyme that maintains telomeres, the protective ends of chromosomes. In most healthy adult cells, TERT is switched off. But if it becomes switched back on, it can fuel cancer development by driving unchecked cell growth.

In this study, the researchers wanted to see whether high TERT expression, even in the absence of the TERT genetic mutation, also predicted worse outcomes. They looked at more than 1,200 meningiomas from patients across Canada, Germany and the U.S., and they found that nearly one-third of them had high TERT expression despite not having the mutation.

These patients had earlier tumor regrowth compared to those without TERT expression, though their outcomes were better than patients with full-blown TERT mutations.

"TERT-positive tumors behaved like they were one grade worse than their official diagnosis," says Dr. Zadeh. "For example, a grade 1 tumor with TERT expression acted more like a grade 2."

Guiding Treatment Decisions

The findings suggest that testing for TERT activity could help doctors predict which patients are at higher risk for recurrence and may need closer monitoring or more intensive treatment.

"Because meningiomas are the most common primary brain tumor, this biomarker could influence how thousands of patients are diagnosed and managed worldwide," says Dr. Zadeh.

"TERT expression can help us more accurately identify patients with aggressive meningiomas," Chloe Gui, M.D., a neurosurgery resident at the University of Toronto, a Mayo Clinic research collaborator and the study’s lead author, explains on a podcast hosted by The Lancet Oncology. "This information allows us to offer treatment tailored to the tumor's behavior."

The team is currently investigating ways to incorporate TERT expression into the clinical workflow. The research is part of a larger effort at Mayo Clinic called the Precure initiative, focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding.