Total copy number for 19 amplified genes in atypical/aggressive meningiomas correlates inversely with patient age

Our aim was to identify genes in meningiomas whose gain in copy number (CN) indicate aggressiveness, using tumor grade and patient age. 78 genes were analyzed in atypical/aggressive (Grade II/III) meningiomas with multiplex ligation‐dependent probe amplification. Among 94 patients (pts), 91 with 105 meningiomas had histological confirmation. Tumors from 17 pts (23–85 yrs, M:F=9:8) were Grade II/III based on having 4 or more mitoses/10 HPF, brain encroachment, aggressive variants or at least 3 moderate subjective features. Compared to Grade I, Grade II/III meningiomas had 9.27‐fold increased mitoses and enhanced architectural sheeting, hypercellularity, macronucleoli, necrosis, small cell change & anaplasia, 2.40, 1.66, 4.08, 4.78, 5.10 & 2.10‐fold, respectively. Tumor DNA samples from 15 pts and normal brain DNA (NB) were analyzed. Increased CN ( 2.0 NB levels) occurred in each tumor for 2 or more of 19 genes (AURKA, BCAS2, BCL6, BCL2A1, BCL2L1, BIRC1/NAIP, BIRC2, BIRC4, BRAF, EGFR, EVI1, GNAS, MDM2, MET, MMP7, NRAS, PIK3CA, PPM1D & RNF139). Each was amplified in multiple tumors. The sum of CN for 19 genes, 25.1 – 49.1, correlated inversely with patient age (r = −0.72), minus an outlier. Characteristic losses at 22q11, 1p34.2 & 1p22.1 loci occurred in >50%. Gains in CN of 19 genes in Grade II/III meningiomas were higher in younger adults with their total sum representing a putative score of aggressiveness. Funded by LSUHSC‐S Grant‐In‐Aid.