Analysis of point mutations and copy number variation in Grade II and III meningioma

Abstract

Meningiomas are among the most common tumors of the adult central nervous system (CNS). They are classified by the World Health Organization into three pathologic grades with increasing severity: grade I are benign with favorable treatment outcomes and low recurrence rates while grade III display malignant behavior and poor progression-free survival. Previous studies have shown that inactivation of NF-2 is the most common genetic event in high-grade meningioma; however, there is dearth of molecular data to distinguish grade II (AM-II) from the even more aggressive grade III (AM-III). As part of a routine diagnostic workup, 19 AM-II and 5 AM-III were submitted for targeted sequencing on a panel of twenty-four genes relevant to CNS tumors. The data generated during the course of clinical care was collected and re-analyzed with the aim of identifying molecular features to distinguish AM-II and AM-III. Our cases contained several well-characterized, potentially actionable mutations, but we did not find any novel, recurrent sequence variants. Copy number variations were common in both AM-II and AM-III; chr22q loss was the most prevalent followed in decreasing frequency by losses of chr1p, chr14q, and chr10. In particular, chr10 loss was noted in 4 of 5 AM-III cases but none of the AM-II cases. This suggests that chr10 loss may serve as a diagnostic and perhaps a prognostic marker to differentiate AM-II from AM-III. If confirmed in larger studies, our finding could further aid the classification of meningioma.