PS6K amplification characterizes a small subset of anaplastic meningiomas.
PS6K, a putative oncogene mapped to chromosome 17q23, encodes a serine/threonine kinase, which phosphorylates ribosomal subunit 6 and is part of the insulin receptor signal transduction pathway involved in the regulation of messenger RNA translation, protein synthesis, cell cycle progression, and cell size. Comparative genomic hybridization studies have detected 17q23 amplifications in a subset of meningiomas, particularly those with aggressive histologic features. PS6K amplifications have been reported in breast cancer, another hormonally driven neoplasm. We assessed PS6K dosage in 94 archival paraffin-embedded meningiomas using dual-color fluorescence in situ hybridization. We found high-level PS6K amplifications in 3 of 22 anaplastic grade III meningiomas. Amplification was confirmed by differential polymerase chain reaction in 1 of these cases. In contrast, no amplifications were identified in 37 benign (grade I) and 35 atypical (grade II) meningiomas. To our knowledge, this represents the first report of gene amplification in primary human meningiomas. Given its exclusive association with anaplastic meningiomas, PS6K amplification likely occurs during the malignant progression of a small subset of anaplastic tumors. Further studies are needed to map the 17q23 amplicon to determine whether additional genes in this region are amplified in high-grade meningiomas.
Cai
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Department of Pathology, Washington University School of Medicine, 660 S Euclid Ave, Box 8118, St Louis, MO 63110, USA.
James
C D
CD
Scheithauer
B W
BW
Couch
F J
FJ
Perry
A
A
D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008577:Meningeal Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*; D008579:Meningioma / Q000145:classification / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D010940:Plant Proteins; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D004273:DNA, Neoplasm; D010940:Plant Proteins; C094467:PSK6 protein, Petunia x hybrida; D017346:Protein Serine-Threonine Kinases