PS6K amplification characterizes a small subset of anaplastic meningiomas

PS6K, a putative oncogene mapped to chromosome 17q23, encodes a serine/thre onine kinase, which phosphorylates ribosomal subunit 6 and is part of the i nsulin receptor signal transduction pathway involved in the regulation of m essenger RNA translation, protein synthesis, cell cycle progression, and ce ll size. Comparative genomic hybridization studies have detected 17q23 ampl ifications in a subset of meningiomas, particularly those with aggressive h istologic features. PS6K amplifications have been reported in breast cancel ; another hormonally driven neoplasm. We assessed PS6K dosage in 94 archiva l paraffin-embedded meningiomas using dual-color fluorescence in situ hybri dization. We found high-level PS6K amplifications in 3 of 22 anaplastic gra de III meningiomas. Amplification was confirmed by differential polymerase chain reaction in I of these cases. In contrast, no amplifications were ide ntified in 37 benign (grade I) and 35 atypical (grade II) meningiomas. To o ur knowledge this represents the first report of gene amplification in prim ary human meningiomas. Given its exclusive association with anaplastic meni ngiomas, PS6K amplification likely occurs during the malignant progression of a small subset of anaplastic tumors. Further studies are needed to map t he 17q23 amplicon to determine whether additional genes in this region are amplified in high-grade meningiomas.