DNA methylation profiling of incidental meningiomas

Methods

A cohort of incidental meningiomas from consecutive patients who presented to a neurosurgical clinic at a single institution were analyzed using serial magnetic resonance imaging volumetrics, IMPACT risk groups, targeted gene expression profiling, DNA methylation profiling, and copy number profiling. All adult patients with asymptomatic, incidental intracranial meningioma on imaging examination were included. Volumetric growth, treatment-free survival, and symptom-free survival from time of detection were compared using the Kaplan-Meier method, Cox proportional hazards regression, and competing risks regression analyses.

Results: The study cohort was comprised of 238 consecutive incidental meningiomas, 81% from women with a median age at detection of 59 years. Median meningioma volume at detection was 3.83 cm3, median annual and percent volumetric growth rate were 0.3 cm3 and 19.7%, respectively, median volumetric doubling time was 4.3 years, and the median clinical and MRI follow-up were 9.1 and 6.7 years, respectively. The rate of symptomatic progression was 15.5%, and 93.7% of incidental meningiomas were treated during follow-up, with a median time-to-treatment of 1.06 years.

IMPACT risk groups stratified treatment-free (p<0.0001) and symptom-free survival (p=0.0007), and only 5% of incidental meningiomas recurred after treatment. Targeted gene expression profiling and DNA methylation profiling revealed that most incidental meningiomas were low molecular risk, although incidental meningiomas from the Hypermitotic DNA methylation group were larger at the time of detection (p=0.0237). Cell cycle genes were suppressed in incidental meningiomas compared to 1434 previously-published non-incidental meningiomas, and incidental meningiomas showed lower copy number alteration burden and distinct patterns of chromosomal alteration compared to non-incidental meningiomas.

Molecular high-risk incidental meningiomas had favorable postoperative outcomes compared to propensity-matched non-incidental meningiomas from the same molecular groups. Conclusions: Incidental meningiomas have excellent clinical outcomes after treatment but are overwhelmingly molecularly low risk and slow growing. These data indicate that the majority of incidental meningiomas can be safely followed with serial imaging surveillance.

Molecular profiling of incidental meningiomas sheds light on early stages of meningeal tumorigenesis and suggests that early treatment of appropriately selected patients may improve long-term clinical outcomes for molecularly high-risk incidental meningiomas.