title: Gene expression, signal transduction pathways and functional networks associated with growth of sporadic vestibular schwannomas.
abstract: The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software. Differential gene expression was defined as a 1.5-fold difference between fast and slow growing tumors (><0.5 ccm/year), employing a p-value <0.01. Deregulated transcripts were matched against established gene ontology. Ingenuity Pathway Analysis was used for identification of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell differentiation and proliferation, among other functions. Fourteen pathways were associated with tumor growth. Five functional molecular networks were generated. This first study on global gene expression in relation to vestibular schwannoma growth rate identified several genes, signal transduction pathways and functional networks associated with tumor progression. Specific genes involved in apoptosis, cell growth and proliferation were deregulated in fast growing tumors. Fourteen pathways were associated with tumor growth. Generated functional networks underlined the importance of the PI3K family, among others.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery and Audiology, Copenhagen University Hospital Rigshospitalet, Boyesgade 5A, st.th, 1622 KBH V, Copenhagen, Denmark. Hjaltesass@gmail.com.
authors.forename: Hjalte C R
authors.initials: HC
authors.lastname: Sass
authors.affiliation: Center for Genomic Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Rehannah
authors.initials: R
authors.lastname: Borup
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery and Audiology, Copenhagen University Hospital Rigshospitalet, Boyesgade 5A, st.th, 1622 KBH V, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Alanin
authors.affiliation: Center for Genomic Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark.
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery and Audiology, Copenhagen University Hospital Rigshospitalet, Boyesgade 5A, st.th, 1622 KBH V, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Cayé-Thomasen
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism; D009464:Neuroma, Acoustic / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger
keywords: Acoustic neuroma; Gene ontology; Ingenuity pathway analysis; Molecular biology