Deregulated genes in sporadic vestibular schwannomas

Per Cayé-Thomasen; Rehannah Holga Andrea Helweg-Larsen; Sven-Eric Stangerup; Jens Christian Thomsen; Finn Cilius Nielsen

doi:10.1097/mao.0b013e3181be6478

Deregulated genes in sporadic vestibular schwannomas

Per Cayé-Thomasen, Rehannah Holga Andrea Helweg-Larsen, Sven-Eric Stangerup, Jens Christian Thomsen, Finn Cilius Nielsen

29 Citationer (Scopus)

Abstract

Objective: In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology. Material and Methods: RNA was extracted from 3 vestibular nerves (serving as control) and 16 solid, sporadic vestibular schwannomas. RNA (5 μg) was used in the labeling and biotinylation protocol to produce cRNA, which was hybridized to Affymetrix HG-U133A arrays. Data were imported into dChip v.1.3 and normalized using invariant set normalization. Differentially expressed genes were identified as differences between control and tumor tissue larger than 2-fold, with a conservative p value of less than 0.000161 and means of differences greater than 25. Results: Eighty-seven probe sets, representing 78 genes, were significantly up- or down-regulated in tumor tissue. The deregulated genes were matched against established gene ontology, revealing that 8 of the up-regulated genes are involved in regulation of the cell cycle, 6 in cell morphogenesis, 8 in cell development, 11 in cell differentiation, 6 in cell death, 13 in cell adhesion, 9 in extracellular matrix, and 50 in protein binding (overlapping occurring). Gene annotation enrichment analyses of the clustered genes showed significant enrichment of annotations for the extracellular matrix (p < 0.0002), cell adhesion (p < 0.0001), and protein binding (p < 0.0004). Conclusion: We conclude that a number of transcripts are deregulated in sporadic vestibular schwannomas, and that several of these have functional annotations implicated in tumorigenesis. Specifically, genes involved in extracellular matrix function, cell adhesion, and protein binding seem to be of potential importance. However, further studies using other methodologies are needed for verification of the observed changes of gene expression seen by cDNA microarray analyses, for example, reverse-transcriptase-polymerase chain reaction and protein analyses.

Originalsprog	Engelsk
Tidsskrift	Otology & Neurotology
Vol/bind	31
Udgave nummer	2
Sider (fra-til)	256-66
Antal sider	11
ISSN	1531-7129
DOI	https://doi.org/10.1097/mao.0b013e3181be6478
Status	Udgivet - 1 feb. 2010

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10.1097/mao.0b013e3181be6478

Citationsformater

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title = "Deregulated genes in sporadic vestibular schwannomas",

abstract = "Objective: In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology. Material and Methods: RNA was extracted from 3 vestibular nerves (serving as control) and 16 solid, sporadic vestibular schwannomas. RNA (5 μg) was used in the labeling and biotinylation protocol to produce cRNA, which was hybridized to Affymetrix HG-U133A arrays. Data were imported into dChip v.1.3 and normalized using invariant set normalization. Differentially expressed genes were identified as differences between control and tumor tissue larger than 2-fold, with a conservative p value of less than 0.000161 and means of differences greater than 25. Results: Eighty-seven probe sets, representing 78 genes, were significantly up- or down-regulated in tumor tissue. The deregulated genes were matched against established gene ontology, revealing that 8 of the up-regulated genes are involved in regulation of the cell cycle, 6 in cell morphogenesis, 8 in cell development, 11 in cell differentiation, 6 in cell death, 13 in cell adhesion, 9 in extracellular matrix, and 50 in protein binding (overlapping occurring). Gene annotation enrichment analyses of the clustered genes showed significant enrichment of annotations for the extracellular matrix (p < 0.0002), cell adhesion (p < 0.0001), and protein binding (p < 0.0004). Conclusion: We conclude that a number of transcripts are deregulated in sporadic vestibular schwannomas, and that several of these have functional annotations implicated in tumorigenesis. Specifically, genes involved in extracellular matrix function, cell adhesion, and protein binding seem to be of potential importance. However, further studies using other methodologies are needed for verification of the observed changes of gene expression seen by cDNA microarray analyses, for example, reverse-transcriptase-polymerase chain reaction and protein analyses.",

author = "Per Cay{\'e}-Thomasen and Helweg-Larsen, {Rehannah Holga Andrea} and Sven-Eric Stangerup and Thomsen, {Jens Christian} and Nielsen, {Finn Cilius}",

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AU - Cayé-Thomasen, Per

AU - Helweg-Larsen, Rehannah Holga Andrea

AU - Stangerup, Sven-Eric

AU - Thomsen, Jens Christian

AU - Nielsen, Finn Cilius

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N2 - Objective: In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology. Material and Methods: RNA was extracted from 3 vestibular nerves (serving as control) and 16 solid, sporadic vestibular schwannomas. RNA (5 μg) was used in the labeling and biotinylation protocol to produce cRNA, which was hybridized to Affymetrix HG-U133A arrays. Data were imported into dChip v.1.3 and normalized using invariant set normalization. Differentially expressed genes were identified as differences between control and tumor tissue larger than 2-fold, with a conservative p value of less than 0.000161 and means of differences greater than 25. Results: Eighty-seven probe sets, representing 78 genes, were significantly up- or down-regulated in tumor tissue. The deregulated genes were matched against established gene ontology, revealing that 8 of the up-regulated genes are involved in regulation of the cell cycle, 6 in cell morphogenesis, 8 in cell development, 11 in cell differentiation, 6 in cell death, 13 in cell adhesion, 9 in extracellular matrix, and 50 in protein binding (overlapping occurring). Gene annotation enrichment analyses of the clustered genes showed significant enrichment of annotations for the extracellular matrix (p < 0.0002), cell adhesion (p < 0.0001), and protein binding (p < 0.0004). Conclusion: We conclude that a number of transcripts are deregulated in sporadic vestibular schwannomas, and that several of these have functional annotations implicated in tumorigenesis. Specifically, genes involved in extracellular matrix function, cell adhesion, and protein binding seem to be of potential importance. However, further studies using other methodologies are needed for verification of the observed changes of gene expression seen by cDNA microarray analyses, for example, reverse-transcriptase-polymerase chain reaction and protein analyses.

AB - Objective: In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology. Material and Methods: RNA was extracted from 3 vestibular nerves (serving as control) and 16 solid, sporadic vestibular schwannomas. RNA (5 μg) was used in the labeling and biotinylation protocol to produce cRNA, which was hybridized to Affymetrix HG-U133A arrays. Data were imported into dChip v.1.3 and normalized using invariant set normalization. Differentially expressed genes were identified as differences between control and tumor tissue larger than 2-fold, with a conservative p value of less than 0.000161 and means of differences greater than 25. Results: Eighty-seven probe sets, representing 78 genes, were significantly up- or down-regulated in tumor tissue. The deregulated genes were matched against established gene ontology, revealing that 8 of the up-regulated genes are involved in regulation of the cell cycle, 6 in cell morphogenesis, 8 in cell development, 11 in cell differentiation, 6 in cell death, 13 in cell adhesion, 9 in extracellular matrix, and 50 in protein binding (overlapping occurring). Gene annotation enrichment analyses of the clustered genes showed significant enrichment of annotations for the extracellular matrix (p < 0.0002), cell adhesion (p < 0.0001), and protein binding (p < 0.0004). Conclusion: We conclude that a number of transcripts are deregulated in sporadic vestibular schwannomas, and that several of these have functional annotations implicated in tumorigenesis. Specifically, genes involved in extracellular matrix function, cell adhesion, and protein binding seem to be of potential importance. However, further studies using other methodologies are needed for verification of the observed changes of gene expression seen by cDNA microarray analyses, for example, reverse-transcriptase-polymerase chain reaction and protein analyses.

U2 - 10.1097/mao.0b013e3181be6478

DO - 10.1097/mao.0b013e3181be6478

M3 - Journal article

SN - 1531-7129

VL - 31

SP - 256

EP - 266

JO - Otology and Neurotology

JF - Otology and Neurotology

IS - 2

ER -

Deregulated genes in sporadic vestibular schwannomas

Abstract

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