title: Meningiomas and schwannomas: molecular subgroup classification found by expression arrays.
abstract: Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.
authors.affiliation: Unidad de Investigación, Hospital Universitario La Paz, 28046 Madrid, Spain. vmartinezg.hulp@salud.madrid.org
authors.forename: Victor
authors.initials: V
authors.lastname: Martinez-Glez
authors.forename: Carmen
authors.initials: C
authors.lastname: Franco-Hernandez
authors.forename: Luis
authors.initials: L
authors.lastname: Alvarez
authors.forename: Jose M
authors.initials: JM
authors.lastname: De Campos
authors.forename: Alberto
authors.initials: A
authors.lastname: Isla
authors.forename: Jesus
authors.initials: J
authors.lastname: Vaquero
authors.forename: Luis
authors.initials: L
authors.lastname: Lassaletta
authors.forename: Cacilda
authors.initials: C
authors.lastname: Casartelli
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rey
mesh_terms: D000328:Adult; D000368:Aged; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000145:classification / Q000235:genetics*; D008579:Meningioma / Q000145:classification / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009442:Neurilemmoma / Q000145:classification / Q000235:genetics*; D016518:Neurofibromatosis 2 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D018076:DNA, Complementary; D004273:DNA, Neoplasm