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Total copy number for 19 amplified genes in atypical/aggressive meningiomas correlates inversely with patient age
Author(s) -
Beckner Marie E,
Sampath Raghuram,
Flowers Ashley B,
Katira Kristopher,
D'Souza Dwain,
Patil Shashikant,
Patel Raj B,
Nordberg Mary L,
Nanda Anil
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.441.9
Subject(s) - copy number variation , gene , genetics , biology , genome
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.