Epigenome analysis of schwannomas arising as part of segmental schwannomatosis due to somatic mosaic SOX10 indel mutations
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE239715 | GEO | 2023/10/11
REPOSITORIES: GEO
Similar Datasets
Project description:Genome-wide DNA methylation profiling of 22 schwannomas belonging to three different genotypes (NF2-mutant, SOX10-mutant, and HTRA1-fused). The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of 22 schwannomas.
2023-07-13 | GSE197094 | GEO
Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them. In order to find target to fight against vestibular schwannoma, we performed an analysis of gene expression by microarrays.
2013-03-01 | E-GEOD-39645 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) negatively regulate protein-coding genes at the post-transcriptional level and are critical in tumorigenesis. Schwannomas develop from proliferation of dedifferentiated Schwann cells, which normally wrap around nerve fibers to help support and insulate nerves. In this study, we carried out high-throughput miRNA expression profiling of human vestibular schwannomas using an array representing 407 known miRNAs in order to explore the role of miRNAs in tumor growth. Twelve miRNAs were found to be significantly deregulated in tumor samples as compared with control nerve tissue, defining a schwannoma-typical signature. Among these miRNAs, we focused on miR-7 which was one of the most downregulated in these tumors and has several known oncogene targets, including mRNAs for epidermal growth factor receptor (EGFR) and p21-activated kinase 1 (Pak1). We found that overexpression of miR-7 inhibited schwannoma cell growth both in culture and in a xenograft tumor model in vivo, which correlated with downregulation of these signaling pathways. Furthermore, we identified a novel direct target of miR-7, the mRNA for associated cdc42 kinase 1 (Ack1), with the expression levels of miR-7 and Ack1 being inversely correlated in human schwannoma samples. These findings are the first analyzing miRNA profiles of schwannomas and support a “tumor suppressor” function for miR-7 in these tumors by targeting proteins in three major oncogenic pathways, EGFR, Pak1, and Ack1. Moreover, our result also suggest that miR-7 may serve as a potential therapeutic molecule for schwannomas and that drugs which inhibit these signaling pathways could suppress growth of these benign tumors. Schwannoma tumor samples are compared to nerve controls
2010-09-29 | E-GEOD-24390 | biostudies-arrayexpress
Project description:Vestibular Schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of NF2. Transcriptomic alterations, such as the Nrg1/ErbB2 pathway, have been described in Schwannomas. Here, we have performed a whole transcriptomic analysis in 31 vestibular Schwannomas and 9 control nerves in the Affymetrix Gene 1.0ST platform, validated by quantitative Real-Time PCR using TaqMan Low Density Arrays. We performed a mutational analysis of NF2 by PCR/dHPLC and MLPA as well as a microsatellite marker analysis of the loss of heterozygosity of chromosome 22q. The microarray analysis showed that 1516 genes were deregulated, and 48 of the genes were validated by qRT-PCR. At least two genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed one hit and eight tumors showed no NF2 alteration. As conclusion, MET and associated genes such as ITGA4/B6, PLEXNB3/SEMA5 and CAV1 showed a clear deregulation in vestibular Schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in Merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in Schwannoma Merlin depletion. Finally, no major differences were found between tumors of different sizes, histological types or NF2 status, which suggests that at the mRNA level all Schwannomas, regardless of molecular and clinical characteristics, may share common features that can be used in the fight against them.
2013-03-01 | GSE39645 | GEO
Project description:MicroRNAs (miRNAs) negatively regulate protein-coding genes at the post-transcriptional level and are critical in tumorigenesis. Schwannomas develop from proliferation of dedifferentiated Schwann cells, which normally wrap around nerve fibers to help support and insulate nerves. In this study, we carried out high-throughput miRNA expression profiling of human vestibular schwannomas using an array representing 407 known miRNAs in order to explore the role of miRNAs in tumor growth. Twelve miRNAs were found to be significantly deregulated in tumor samples as compared with control nerve tissue, defining a schwannoma-typical signature. Among these miRNAs, we focused on miR-7 which was one of the most downregulated in these tumors and has several known oncogene targets, including mRNAs for epidermal growth factor receptor (EGFR) and p21-activated kinase 1 (Pak1). We found that overexpression of miR-7 inhibited schwannoma cell growth both in culture and in a xenograft tumor model in vivo, which correlated with downregulation of these signaling pathways. Furthermore, we identified a novel direct target of miR-7, the mRNA for associated cdc42 kinase 1 (Ack1), with the expression levels of miR-7 and Ack1 being inversely correlated in human schwannoma samples. These findings are the first analyzing miRNA profiles of schwannomas and support a “tumor suppressor” function for miR-7 in these tumors by targeting proteins in three major oncogenic pathways, EGFR, Pak1, and Ack1. Moreover, our result also suggest that miR-7 may serve as a potential therapeutic molecule for schwannomas and that drugs which inhibit these signaling pathways could suppress growth of these benign tumors.
2010-09-29 | GSE24390 | GEO
Project description:SpCas9 INDEL frequency and HITI was evaluated at the on-target site of guide RNA targeting either the mouse or pig rhodopsin by next-generation sequencing.
2021-11-11 | GSE180875 | GEO
Project description:This work uses cDNA microarray technology to establish expression patterns of 96 cancer related genes on 42 meningiomas and 23 schwannomas.
2008-09-01 | E-MTAB-15 | biostudies-arrayexpress
Project description:Background: Schwannomas and grade I meningiomas are non-metastatic neoplasms that shares the common mutation of gene NF2. They usually appear in Neurofibromatosis type 2 patients. Currently, there is no drug treatment available for both tumors, so the use of wide expression technologies is crucial to find those therapeutic targets. Methodology: Affymetrix Human Gene 1.0 ST was used to test global gene expression in 22 meningiomas, 31 schwannomas and, as non-tumoral controls, 3 healthy meningeal tissues, 8 non-tumoral nerves and 1 primary Schwann cells culture. A non-stringent P-cutoff and fold change were used to establish deregulated genes. Results and discussion: We found a subset of genes that were upregulated in meningiomas and schwannomas when compared to their respectively healthy tissue, including PDGFD, CDH1, SLIT2 and MET. Thus, those genes could be more thoroughly studied as targets in a possible combined treatment. Methodology: Affymetrix Human Gene 1.0 ST was used to test global gene expression in 22 meningiomas, 31 schwannomas and, as non-tumoral controls, 3 healthy meningeal tissues, 8 non-tumoral nerves and 1 primary Schwann cells culture. A non-stringent P-cutoff and fold change were used to establish deregulated genes.
2015-08-30 | E-GEOD-54934 | biostudies-arrayexpress
Project description:SpCas9 INDEL frequency was evaluated at both the on- and off-target sites of guideRNA targeting either the murine Rhodopsin or Albumin by Next Generation Sequencing. Minimal INDELs were found at the off target sites evaluted, while SpCas9 activity was predominantly on-target.
2021-11-11 | GSE180117 | GEO
Project description:Background: Vestibular Schwannomas are benign tumors that arise from Schwann cells in the VIII cranial pair and usually present NF2 gene mutations and/or loss of heterozygosity on chromosome 22q. Deregulation has also been found in several genes, such as ERBB2 and NRG1. MicroRNAs are non-coding RNAs approximately 21 to 23 nucleotides in length that regulate mRNAs, usually by degradation at the post-transcriptional level. Methods: We used microarray technology to test the deregulation of miRNAs and other non-coding RNAs present in GeneChip miRNA 1.0 (Affymetrix) over 16 vestibular Schwannomas and 3 control-nerves, validating 10 of them by qRT-PCR. Findings: Our results showed the deregulation of 174 miRNAs, including miR-10b, miR-206, miR-183 and miR-204, and the upregulation of miR-431, miR-221, miR-21 and miR-720, among others. The results also showed an aberrant expression of other non-coding RNAs. We also found a general upregulation of the miRNA cluster located at chromosome 14q32. Conclusion: Our results suggest that several miRNAs are involved in tumor formation and/or maintenance and that global upregulation of the 14q32 chromosomal site may represent a therapeutic target for this neoplasm. 16 Vestibular Schwannomas and 3 control-nerves were analysed
2014-03-24 | E-GEOD-43571 | biostudies-arrayexpress