title: Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas.
abstract: The majority of meningiomas are probably benign but a number of tumors display considerable histological and/or clinical aggressivity, sometimes with unexpectedly high recurrence rates after radical removal. Understanding the potential behavior of these tumors in individual patients is critical for rational therapeutic decision-making. This study aimed to identify gene expression profiles and candidate markers associated with original and recurrent meningiomas. Unsupervised hierarchical clustering of the samples confirmed 2 main groups of meningiomas with distinct clinical behaviors. The gene expression profiling study identified genes and pathways potentially associated with meningioma recurrence, revealing an overall lower level of gene expression. The differential gene expression profiling analyses of original and recurrent meningiomas identified 425 known genes and expressed sequence tags related to meningioma recurrence, with SFRP1 (8p12), TMEM30B (14q23), and CTGF (6q23) showing the most disparate expression. Most of the differentially expressed genes were located at 1p, 6q, and 14q and were underexpressed in recurrences. Loss of such chromosomal regions has previously been associated with a higher risk of meningioma recurrence or malignant progression. Thus, at these locations, we propose the existence of novel candidate genes that could be involved in meningioma recurrence. In addition, the overexpression of genes of histone cluster 1 (6p) in recurrent meningiomas is reported here for the first time. Finally, the altered genes related to meningioma recurrence are involved in pathways such as Notch, TGFβ, and Wnt, as described previously, and in other pathways such as cell cycle, oxidative phosphorylation, PPAR, and PDGF, not related before to meningioma recurrence.
authors.affiliation: Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo 45004, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pérez-Magán
authors.forename: Angel
authors.initials: A
authors.lastname: Rodríguez de Lope
authors.forename: Teresa
authors.initials: T
authors.lastname: Ribalta
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Ruano
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos-Martín
authors.forename: Gerardo
authors.initials: G
authors.lastname: Pérez-Bautista
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: García
authors.forename: Ainoha
authors.initials: A
authors.lastname: García-Claver
authors.forename: Concepción
authors.initials: C
authors.lastname: Fiaño
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Hernández-Moneo
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.forename: Bárbara
authors.initials: B
authors.lastname: Meléndez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006657:Histones / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones