Microarray-Based Analysis of Spinal versus Intracranial Meningiomas: Different Clinical, Biological, and Genetic Characteristics Associated with Distinct Patterns of Gene Expression

• Published in: Journal of neuropathology and experimental neurology Vol. 65; no. 5; pp. 445 - 454
• Main Authors: Sayagués, José María, Tabernero, María Dolores, Maíllo, Angel, Trelles, Osvaldo, Espinosa, Ana Belén, Sarasquete, Maria Eugenia, Merino, Marta, Rasillo, Ana, Vera, Jaime Fernandez, Santos-Briz, Angel, de Alava, Enrique, Garcia-Macias, Maria Carmen, Orfao, Alberto
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.05.2006; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Aged; Biological and medical sciences; Chromosome Aberrations; Female; Flow Cytometry - methods; Gene Expression - physiology; Gene Expression Profiling - methods; Humans; In Situ Hybridization, Fluorescence - methods; Male; Medical sciences; Meningeal Neoplasms - genetics; Meningeal Neoplasms - physiopathology; Meningioma - classification; Meningioma - genetics; Meningioma - physiopathology; Middle Aged; Nervous system involvement in other diseases. Miscellaneous; Neurology; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Statistics, Nonparametric; Tumors of the nervous system. Phacomatoses; Intracranial; Nervous system diseases; FISH; Genetics; Spinal meningioma; Benign neoplasm; Gene expression; Microarray; Comparative study; Meningioma
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/01.jnen.0000229234.13372.d8

It has long been recognized that spinal meningiomas show particular clinical and histological features. Here, we compare the clinico-biological characteristics as well as the genetic abnormalities and patterns of gene expression of spinal and intracranial meningiomas. Fourteen spinal and 141 intracranial meningioma patients were analyzed at diagnosis. In all tumors, interphase fluorescence in situ hybridization (iFISH) studies were performed for the detection of quantitative abnormalities for 11 different chromosomes. Additionally, microarray analyses were performed on a subgroup of 18 histologically benign meningiomas (7 spinal and 11 intracranial). Upon comparison with intracranial tumors, spinal meningiomas showed a marked predominance of psammomatous and transitional tumors (p = 0.001), together with a higher proportion of cases displaying a single tumor cell clone by iFISH (p = 0.004). In 86% of the spinal versus 56% of the intracranial tumors (p = 0.01), the ancestral tumor cell clone detected showed either absence of any chromosomal abnormality or monosomy 22/22qalone. Analysis of gene expression profiles showed differential expression between spinal and intracranial meningiomas for a total of 1555 genes, 35 of which allowed a clear distinction between both tumor types. Most of these 35 genes (n = 30) showed significantly higher expression among spinal tumors and corresponded to genes involved in signal transduction pathways, which did not show a significantly different expression according to tumor histopathology. In summary, we show the occurrence of unique patterns of genetic abnormalities and gene expression profiles in spinal as compared to intracranial meningiomas that provide new insights into the molecular pathways involved in the tumorigenesis and progression of spinal meningiomas, and could help explain their particular clinical and histological features.