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Published on: February 17, 2023
Association between tumor mutations and meningioma recurrence in Grade I/II disease
Jonathan T Dullea1, Vikram Vasan1, John W Rutland1
1Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 10129, USA.
Background:
Meningiomas are common intracranial tumors with variable prognoses not entirely captured by commonly used classification schemes. We sought to determine the relationship between meningioma mutations and oncologic outcomes using a targeted next-generation sequencing panel.
Materials And Methods:
We identified 184 grade I and II meningiomas with both >90 days of post-surgical follow-up and linked targeted next-generation sequencing. For mutated genes in greater than 5% of the sample, we computed progression-free survival Cox-regression models stratified by gene. We then built a multi-gene model by including all gene predictors with a p-value of less than 0.20. Starting with that model, we performed backward selection to identify the most predictive factors.
Results:
ATM (HR = 4.448; 95% CI: 1.517-13.046), CREBBP (HR = 2.727; 95% CI = 1.163-6.396), and POLE (HR = 0.544; HR = 0.311-0.952) were significantly associated with alterations in disease progression after adjusting for clinical and pathologic factors. In the multi-gene model, only POLE remained a significant predictor of recurrence after adjusting for the same clinical covariates. Backwards selection identified recurrence status, resection extent, and mutations in ATM (HR = 7.333; 95% CI = 2.318-23.195) and POLE (HR = 0.413; 95% CI = 0.229-0.743) as predictive of recurrence.
Conclusions:
Mutations in ATM and CREBBP were associated with accelerated meningioma recurrence, and mutations in POLE were protective of recurrence. Each mutation has potential implications for treatment. The effect of these mutations on oncologic outcomes and as potential targets for intervention warrants future study.
Insights
Meningioma recurrence is linked to ATM and CREBBP mutations, while POLE mutations offer protection. These genetic alterations may guide future treatment strategies for intracranial tumors.
Area of Science:
- Neuro-oncology
- Genetics
- Tumor Biology
Background:
- Meningiomas are common intracranial tumors with unpredictable prognoses.
- Current classification schemes do not fully capture meningioma behavior.
- Investigating genetic mutations can refine outcome prediction.
Purpose of the Study:
- To explore the association between specific gene mutations and oncologic outcomes in meningiomas.
- To identify genetic markers that predict disease progression and recurrence.
- To evaluate the potential of targeted next-generation sequencing in meningioma management.
Main Methods:
- Analysis of 184 grade I and II meningiomas with extended follow-up.
- Targeted next-generation sequencing to identify common mutations.
- Progression-free survival analysis using Cox-regression models.
- Development of a multi-gene predictive model through backward selection.
Main Results:
- ATM and CREBBP mutations correlated with increased meningioma recurrence risk.
- POLE mutations were associated with a reduced risk of recurrence.
- A final model identified recurrence status, resection extent, and ATM/POLE mutations as key predictors.
Conclusions:
- ATM and CREBBP mutations accelerate meningioma recurrence; POLE mutations are protective.
- These genetic findings have implications for personalized meningioma treatment.
- Further research is needed to explore these mutations as therapeutic targets.
