Genomic profiling of sporadic multiple meningiomas

Area of Science:

• Neuro-oncology
• Genomics
• Tumor Biology

Background:

• Multiple meningiomas (MMs) rarely occur sporadically, and the molecular mechanisms of their formation and clonal etiology are poorly understood.
• It remains unclear if individual tumors within a single patient exhibit similar behavior.

Purpose of the Study:

• To investigate the clonal origin and molecular characteristics of sporadic multiple meningiomas.
• To determine if tumors within a single patient share a common clonal origin or arise independently.

Main Methods:

• Comprehensive next-generation sequencing of 15 meningiomas and 1 dural specimen from 6 patients with sporadic MMs.
• Analysis of clinical data, including tumor grade and spatial separation.

Main Results:

• 11/15 tumors were NF2-loss subtype; 5/6 patients had MMs of monoclonal origin.
• One patient showed independent clonal formation, and a novel non-NF2 mutant MM with monoclonal etiology was identified.
• Monoclonal MMs exhibited inter-tumoral heterogeneity due to branched evolution, and Grade I and II meningiomas occurred in the same patient.

Conclusions:

• Both NF2-loss and non-NF2 driven MMs can originate from monoclonal expansion and develop heterogeneity.
• The molecular profile and clinical behavior of one meningioma cannot predict another within the same patient.
• Individualized clinical management strategies are recommended for patients with multiple meningiomas.