Oct. 07, 2025
Researchers co-led by a Mayo Clinic Neurosurgery chair have demonstrated that telomerase reverse transcriptase (TERT) gene expression in meningiomas predicts earlier disease progression, independent of TERT promoter mutations (TPMs) and other markers.
"The findings suggest that TERT might be a more informative biomarker than TPMs, and TERT expression in meningiomas might warrant reclassification to a higher WHO grade," says Gelareh Zadeh, M.D., Ph.D., chair of Neurosurgery at Mayo Clinic in Rochester, Minnesota.
The study, which retrospectively examined clinical and molecular data from 1,241 meningiomas, is the first comprehensive investigation of TERT RNA expression and associated clinical outcome in a multi-institutional cohort of meningiomas. As described in The Lancet Oncology, the researchers analyzed 380 meningiomas from a single center and a validation cohort of 861 meningiomas from institutions across the U.S., Canada and Germany.
TPMs are well-established drivers of cancer biology and are associated with aggressive meningioma behavior. However, the role of TERT expression itself in meningioma is poorly understood. Although TERT expression is characteristic of tumors with TPMs, TERT expression also has been observed in tumors with wild-type promoters.
In this study the researchers found that TPMs are rare in meningiomas, but TERT expression is relatively common. "Approximately one-third of meningiomas in our cohort expressed TERT, while only 2.9% had TPMs," Dr. Zadeh says. "TERT expression also conferred a poorer prognosis across all WHO grades, independent of TPMs."
Over a median follow-up of 6.2 years, TERT expression conferred what the researchers characterize as intermediate progression-free survival: shorter than TERT-negative tumors but longer than tumors with TPMs. Within WHO grading, TERT expression conferred a progression-free survival equivalent to TERT-negative meningiomas of one grade higher.
"For example, grade 2 tumors with TERT expression had progression-free survival resembling that of TERT-negative grade 3 tumors." Dr. Zadeh says.
The researchers also investigated the relationship among TERT promoter methylation, TPMs and TERT expression. "We observed that TERT promoter methylation and TPM may act as complementary processes involved in TERT reactivation," Dr. Zadeh says.
The researchers note that it remains uncertain whether increased TERT expression in meningiomas directly contributes to poorer clinical outcome or reflects a bystander effect. Previous studies have identified telomerase activity as a marker of higher grade meningiomas, suggesting that TERT — a telomerase component — might play a functional role in tumor aggressiveness.
"Future work that correlates TERT expression with telomerase activity will be essential to clarify TERT's biological significance," Dr. Zadeh says. "Additional work investigating genomic mechanisms that drive TERT expression are also warranted."
For more information
Gui C, et al. Analysis of TERT association with clinical outcome in meningiomas: A multi-institutional cohort study. The Lancet Oncology. 2025;26:1191.
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